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.

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.

At the end of the movie, Henry made a video for Lucy to let her know what had happened since the accident that caused her memory loss. In the video, Henry said on one card, "Red Sox win Series!" The next card read "Just kidding." The movie came out in February 2004. Later that year, the Red Sox actually broke an 86-year drought and won the World Series. Drew Barrymore was actually on the field after the win while filming scenes for Fever Pitch (2005).

The book Lucy reads at breakfast, "Still Life With Woodpecker - A Sort Of A Love Story" by Tom Robbins, is a love story set in Hawaii.

Originally entitled "50 First Kisses" but changed to avoid confusion with Drew Barrymore's vehicle Never Been Kissed (1999).

This movie spoils the ending of The Sixth Sense (1999).

Ula's "huge back swing" which Henry (Adam Sandler) calls "the stupidest flippin' swing I've ever seen" was inspired by Happy's (Adam Sandler) swing in Happy Gilmore (1996).

Blake Clark, who is a Vietnam Veteran with the US Army, wears a hat from the USS Badger (DE 1071) named after Admiral Oscar C. Badger II, Charles J. Badger's son (1890-1958), was the first Navy officer to step ashore in Japan at the end of World War II and was also awarded the Naval Medal of Honor.

Maya Rudolph makes an appearance in this movie as Lucy's pregnant friend. She would later go on to star in Grown Ups (2010) alongside Adam Sandler and Rob Schneider but plays Chris Rock's pregnant wife.

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.

Of the three movies Adam Sandler and Drew Barrymore made together, this is the only one that was #1 at the box office and made over $100 million in theaters.

The original script set the movie in Seattle, the hometown of scriptwriter George Wing.

"Jocko" was played by Sivuqaq, one of four walruses living at Six Flags Marine World in Vallejo, CA. The three female walruses featured in the film are named Siku, Uquq and Qiluk.

Inspiration for this film was taken from Harold Ramis' romantic comedy Groundhog Day (1993).

When Henry and Lucy are first at his place they see two dolphins that Henry names after Mary-Kate Olsen and Ashley Olsen.

Hold me now by the Thompson Twins can be heard in both 50 First Dates and The Wedding Singer, both movies have Adam Sandler and Drew Barrymore as their lead actors/actress.

The beach used in the love scene with Henry and Lucy is the same one that Deborah Kerr and Burt Lancaster used in From Here to Eternity.

While Henry, Ula, and all of his kids are golfing, Ula's kids run up to the golf ball to drive it. This is a trademark from Happy Gilmore (1996), another Adam Sandler movie. That's how he drives the ball.

Both Henry and Doug had relationship issues with a girl named "Tracy", Henry during college and Doug in high school.

The Minnesota Vikings football game Marlin and Doug watch was the Vikings playing against the Detroit Lions on October 13, 2002. The Vikings beat the Lions 31-24.

The only pairing of Adam and Drew directed by Peter Segal. The other two were directed by Frank Coraci.

Actor/Producer Anthony Begonia was set to play a cameo as an ukulele player but was unavailable.

Drew Barrymore's character in Ever After was also in love with a Henry, though he was a prince, not a vet.

Henry and Lucy's daughter is named Nicole.