The neurological condition that Lucy suffers from, Goldfield Syndrome, is entirely fictional. True anterograde amnesia affects either short-term memory, which can last minutes or seconds, or intermediate-term memory, which can last days or weeks. Falling asleep has nothing to do with the condition, and sleep actually intensifies many chemical effects which help memory.
In an early scene a dentist and a woman in the dentist's chair are seen talking with each other. The woman playing the dentist is Jackie Sandler, Adam Sandler's wife. And the woman in the chair is played by Linda Segal, director Peter Segal's wife, who actually is a dentist in real life.
Henry makes a video for Lucy to remind her of the events that have occurred since her accident. One of the items is "Red Sox win the World Series..." followed by "... Just Kidding". During the year of the film's release, the Red Sox actually broke an 86-year drought and won the World Series. Drew Barrymore made the movie Fever Pitch (2005) about an avid Red Sox fan and they filmed the final scene on the Busch Stadium field while the Red Sox celebrated winning the 2004 World Series.
The clinic that Lucy visits is called the "Callahan Institute" and Dr. Keats (Dan Aykroyd) states that it is "funded out of Sandusky, Ohio by T.B. Callahan, the automotive components tycoon". In Tommy Boy (1995), Aykroyd plays a rival automotive components tycoon that is attempting to purchase Tom (T.B.) Callahan's company.
The diner where Lucy has her breakfast every morning was originally a house that was remodeled for the movie. It is located on a macadamia nut farm on the eastern side of Oahu. The same house was used in Tears of the Sun (2003) and scenes from Jurassic Park (1993) were filmed in the open fields nearby.
Rob Schneider's character Ula was inspired by Siope Samuela Ula Lomu, a Tongan concierge at a luxury rental property at which Schneider, Adam Sandler and Drew Barrymore are regular visitors. Lomu has the same blinded, grayed-over left eye that Schneider's Ula has, but there's not much resemblance beyond that. Says Lomu, "They aren't like some other top Hollywood people. They're really normal."
There are several references to the Hormel meat product Spam in the movie. According to Hormel, Hawaii leads the nation in per capita consumption of Spam. Over 6.7 million cans are sold annually in Hawaii, which equals 5.5 cans per year per Hawaiian.