Natalee Ann Holloway was born on 21 October 1986 in Clinton, Mississippi to David Edward and Elizabeth Ann Holloway. Her parents divorced in 1993, and Natalee lived with her mother and younger brother. Elizabeth remarried to George Twitty, a prominent Alabama businessman in 2000.

Natalee graduated with honors from Mountain Brook High School in Alabama. Additionally, she was a member of the National Honor Society and her school's dance team. She planned to attend the University of Alabama in the fall of 2005 when she went missing in May of 2005 in Aruba during a high school graduation trip.

Holloway was seen last by her classmates when she left Carlos'n Charlie's night club around 1:30 a.m. on Monday, 30 May 2005. She left with 17-year-old Joran van der Sloot, a Dutch honors student who lived in Aruba and his two Surinamese friends, 21-year-old Deepak Kalpie and 18-year-old Satish Kalpoe. When Halloway did not return for her flight home and her luggage and passport were found in her room later that day, Aruban authorities initiated searches for her throughout the island and surrounding waters, but did not find her.

That same Monday, Holloway's mother and stepfather flew to Aruba on a private jet to conduct their own search. They found Van der Sloot and confronted him to no avail. In fact, over the following years, Van Der Sloot would recreate his story over and over, was arrested twice and released. Many other individuals were arrested, detained and questioned in Aruba and in the Netherlands. After all the questioning and physical evidence examined, it appears that Holloway had disappeared into thin air.

This story, much like the coverage of O.J. Simpson's trial, received heavy media coverage. Authorities from Aruba, the U.S., and Dutch National Police have been involved with the investigation on and off over the years. The latest attempt to find Natalee has been in March 2009, when her natural father, David Holloway, flew a search dog to Aruba to search a small reservoir in northern Aruba previously identified by a supposed witness as a possible location of Natalee's remains.