In recent years, only a handful of missing persons cases have generated a media sensation in the US, comparable to that which followed the 2005 disappearance of 18 year-old Natalee Ann Holloway, a straight-A student from Mountain Brook, Alabama, on the Caribbean island of Aruba.

Natalee was born on October 21, 1986, to Beth and Dave Holloway. She vanished on May 30, 2005, hours before she was to return from Aruba, where she had been celebrating her graduation from Mountain Brook High School, along with 124 classmates and seven chaperones.

For months afterwards, Natalee's disappearance dominated the cable news channels. Tens of millions of Americans quickly became familiar with her name, and the basic elements of the story: Pretty blond teenager vacationing in a tropical paradise, leaves a bar with three young men she has just met, and is never seen again. Even now, three years later, Natalee remains probably the most famous missing American, since Jimmy Hoffa in 1975.

Natalee's classmates last saw her as she was leaving the nightclub Carlos 'n Charlie's in downtown Oranjestad, with a 17 year-old Dutch boy, Joran van der Sloot, and two Surinamese brothers, Deepak and Satish Kalpoe. The four left left in Deepak's car, around closing time at 1:00 am. Natalee and several of her friends had first encountered Joran earlier that night in their hotel casino, where they invited him to meet them at Carlos 'n Charlie's.

Initially all three young men told police that after taking Natalee on a short trip to see a lighthouse, during which she and Joran were kissing in the back seat, they dropped her off in front of her hotel, the Holiday Inn. However, the three now all agree that Natalee actually got out with Joran at the beach by the Marriott hotel, about 500 meters north of the Holiday Inn. Joran claims that he and Natalee then walked further north to a more isolated area, where they engaged in some sexual activity on the beach, but although Natalee wanted to have sex, they did not do so because he did not have a condom. Joran also claims that he left her on the beach, along with his shoes, after she refused to leave. But although Joran says Satish returned to give him a ride home, then volunteered to go back for his shoes, the Kalpoes deny that, and Deepak says Joran told him over the phone, that he was walking home without his shoes. Records show that Joran called Deepak from his cell phone at 2:26 am, sent him the text message "I'm home" at 3:13 am, and was logged onto his home computer at 3:25 am.

Natalee was reported missing later that morning, after she failed to appear to appear for her group flight back to the United States. Her passport, phone, and luggage were all found in her hotel room; the only missing items were those she had on her when she left for Carlos 'n Charlie's.

Hours after Natalee's flight left without her, Beth Holloway flew to Aruba on a donated private jet, along with her then husband George "Jug" Twitty, and several of their friends. With the help of some Aruban citizens, the Alabama group quickly identified Joran as the person Natalee left with, and delivered that information to Aruban police. At about 2:00 am on May 31, they went to the Van der Sloot home, accompanied by police, where they encountered Joran's father Paul, a local judge-in-training. Joran was out gambling, but after a phone call from his father, he returned home with Deepak. During the ensuing confrontation, Joran told the group the fictional Holiday Inn drop off story, to which Deepak added that before they drove away, Natalee had been approached outside the hotel lobby, by a dark man in a security guard uniform.

Later that day, Joran and the Kalpoes each gave formal witness statements to police, in which Satish also claimed to have seen the security guard. According to former Aruban police chief Gerold Dompig, surveilance of the trio, which included phone wiretaps, began on the third day after Natalee was reported missing.

On June 5, 2005, police made their first arrests in the case: Two security guards, Abraham Jones and Antonious "Mickey" John, both of whom matched the general description provided by the Kalpoes (Aruban law allows for suspects to be detained for up to four months without charges, subject to periodic judicial review). The guards were held until June 13.

Joran and the Kalpoes were arrested for the first time on June 9, 2005. The next day, Joran became the first of the three to abandon the Holiday Inn story, claiming instead that the Kalpoes had taken him home, then left with Natalee to take her back to her hotel. On June 11, the Kalpoes told police they had left Joran and Natalee at the beach, and on June 13, Joran changed his story again, so that he and the Kalpoes now agreed on that point. From then through June 19, Joran also claimed that Deepak had picked him up from the beach, but after being confronted with electronic messages contradicting that claim, he switched to saying he was picked up by Satish.

A disc jockey named Steve Croes was arrested on June 17, and held until June 27, as a result of claiming to have witnessed the trio dropping Natalee off at the Holiday Inn. Paul van der Sloot was arrested on June 22, and held until June 26.

On April 15, 2006, Aruban police arrested 19 year-old Geoffery von Cromviort, on suspicion of involvement in the disappearance. He was held until April 26, 2006. The exact reasons for Von Cromviort's detention were never publicly clarified: Apparently he and Joran did not know each other, and according to his attorney, he denied ever meeting Natalee. Another individual with initials "A.B." was arrested on April 22, 2006, but released the same day.

Guido Wever, a friend of Joran and former croupier at the Holiday Inn, was arrested in the Netherlands on May 17, 2006, becoming the tenth person to be detained in the Holloway case. Wever's arrest was based largely on statements given in early 2006, by several witnesses, who claimed he had scratches on his face in the days following the disappearance. However, Wever's attorney disputed those claims, and although Aruban authorities requested his transfer to the island, he was instead released on May 23.

At Aruba's request, a team of Dutch investigators from the Korps Landelijke Politiediensten began reviewing the investigation in September 2006, following receipt of case documentation in the Netherlands. In April 2007, the Dutch team began pursuing the investigation in Aruba.

On November 21, 2007, Joran was re-arrested in the Netherlands, and the Kalpoes were re-arrested in Aruba. On November 23, Joran was transfered from the Netherlands to Aruba. However, a judge ordered the release of both Kalpoes on November 30, 2007, and of Joran on December 7, 2007. Before the end of the year, prosecutors announced they were closing the investigation without filing charges, but that were some significant new evidence to be found, charges could still be brought, within the statute of limitations. According to a prosecution press release, in Aruba the statute of limitations for involuntary manslaughter expires six years from the day after the crime was committed, and for homicide it expires after after 12 years.

On February 3, 2008, the television program of Dutch crime reporter Peter de Vries played portions of secretly recorded conversations between Joran and a man named Patrick van der Eem, who had enticed Joran with a scheme to start a marijuana operation, but who was actually working for De Vries. In those conversations, Joran stated that he had been engaged in consensual sexual activity with Natalee, when she began shaking or convulsing, became unresponsive, and apparently expired, after which he used a pay phone outside the Marriott to call a friend named "Daury Davens". Supposedly, this friend then used his boat to dispose of Natalee at sea, while Joran walked home. However, once the existence of the the tapes became known, Joran declared that his confession was false. Also, it appears that Joran only knew one person named Daury, whose last name is Rodriquez, and who was at school in the Netherlands when Natalee vanished. It is not publicly known whether police have the records from that morning for all pay phones in the Marriott area, and can rule out Joran having called an accomplice from any of them.

Based on the tapes, prosecutors temporarily re-opened the case, and attempted to obtain an arrest warrant for Joran, who submitted to voluntary questioning in the Netherlands on February 8, 2008. The re-arrest request was denied by the examining judge and appeals court, on grounds which included the fact that details of the confession could not be corroborated.

There have been several civil court cases filed in the US, related to the disappearance, or the media coverage thereof. The first was a suit filed by Natalee's parents on February 11, 2006, against Joran and Paul van der Sloot, while Joran was in New York for a televsion interview. The suit alleged that Joran had sexually assaulted Natalee, falsely imprisoned her, and prevented her from returning to her parents, while accusing Paul of failing to supervise Joran. It was dismissed on jurisdictional grounds on August 11, 2006.

On December 14, 2006, the Kalpoes filed a defamation suit in Los Angeles, against television personality Dr. Phillip McGraw. The suit was based on a September 15, 2005 "Dr. Phil" program, featuring a portion of a taped interview with Deepak by private investigator Jaime Skeeters, in which Deepak appeared to respond "She did" to Skeeters' comment, "I'm sure she had sex with all of you." However, a publicly released copy of the original unedited recording shows that Deepak actually responded with a head-shaking "No, she didn't".

Also on December 14, 2006, Natalee's parents filed a wrongful death lawsuit against the Kalpoes, in the same venue. The wrongful death suit was dismised on jurisdictional grounds on June 1, 2007, while the defamation suit remains pending.

On November 24, 2008, the program "On the Record" aired an interview with Joran, taped about 6 months after his November 2007 arrest, in which he alleged that he had been paid to deliver a blond girl to the beach, by an unidentified individual who then took Natalee away alive by boat. Joran also alleged that the Kalpoe brothers had been aware of this plot, that he paid them for their assistance, and that his father had paid off two police officers who learned Natalee had been taken to Venezuela. However, Joran retracted the statements made in the interview, in an e-mail sent to the program hours after it was taped.

Joran's father Paul Van der Sloot died of a heart attack on February 11, 2010. .

On February 28, 2010, a program was broadcast on Netherlands TV channel RTL 5, in which video was shown of Joran taking a polygraph test in April 2009, and of an interview with Joran in September 2009, in which he made another alleged confession. Although during the polygraph test, Joran denied having any involvement in Natalee's death or disappearance, according to the polygraph examiner the results showed that Joran was lying. In the September 2009 interview, Joran claimed that after being dropped off at the Marriott, he and Natalee were walking back to the Holiday Inn, when they met Joran's friend Andre, and walked with him to his nearby house, where after using drugs with Andre, Natalee died from a fall off a balcony. Joran and Andre then allegedly used Andre's car to transport Natalee's body to a swamp, where they buried her. Aruba's new chief prosecutor told NBC news that authorities had investigated this latest story and found it "very unbelievable", because "locations, names and times he gave just did not make sense."

Stephany Flores Ramirez, a 21-year-old Peruvian student, was reported missing on May 30, 2010. Three days later she was found dead in a hotel room in Lima, Peru which was registered to Joran. On June 3, 2010, Joran was arrested in Chile, and he was deported to Peru the next day. On June 5, 2010, portions of hotel security video were publicly released, which showed Joran and Flores entering the room together on the morning of May 30, and Joran leaving alone several hours later. On June 7, 2010, Peruvian authorities said that Joran had confessed to killing Flores, and on June 11, 2010, Joran was charged in Lima Superior Court with first-degree murder and robbery.

On June 3, 2010, Joran was charged in the U.S. District Court of Northern Alabama with wire fraud and extortion for the amount of $25,000, in exchange for information on the location of Natalee's body. According to an affadavit, an advance amount of $15,000 had been wired from Alabama to Joran's account in the Netherlands on May 10, 2010, following Joran's receipt of $10,000 in cash in Aruba. The affadavit also stated that Joran claimed Natalee had died when she tried to prevent him from leaving, he pushed her, and she hit her head on a rock, after which his father buried her beneath a house that was under construction. However, subsequent investigation established that construction of the house identified by Joran had not yet begun at that time, and in a May 17, 2010 e-mail, Joran admitted he had lied about the location of Natalee's remains.