- Told that the script for Legally Blonde (2001) initially came her way but she was leery about taking on another "dumb blonde" role since Married... with Children (1987) had just wrapped. The role eventually went to Reese Witherspoon and she was nominated for the Golden Globe for portraying Elle Woods. Applegate is happy with the way things turned out and said that Witherspoon did a much better job than she ever could.
- Her garage was the birthplace of The Pussycat Dolls.
- In contrast to her character on Married... with Children (1987), she has been described by her co-stars on the sitcom as an intelligent, versatile and talented actress. In multiple interviews, Ed O'Neill stated that only someone of her caliber and intelligence could pull off the "dumb blonde" character on the sitcom so convincingly, and that she would often nail her performance on the first or second take.
- On 8/3/08, People magazine reported that she had been diagnosed with early-stage breast cancer. Benefiting from early detection through a doctor-ordered MRI, the cancer is not life-threatening. She is following the recommended treatment of her doctors and will have a full recovery. On 8/19/08, it was announced that she was cancer-free after a double mastectomy, though cancer was found in only one breast.
- She was awarded a Star on the Hollywood Walk of Fame for Television at 7007 Hollywood Boulevard in Hollywood, California on November 14, 2022. Her Walk of Fame star is located across the street from the Hollywood Roosevelt Hotel.
- Was at the Viper Room the night River Phoenix collapsed on the sidewalk outside the club. She witnessed the seizure induced by a drug Phoenix had in his system and later re-enacted the seizure at an anti-drugs dance piece.
- She and Bruce Willis are the only two actors to have guest-starred on Friends (1994) and win an Emmy Award for their performance.
- Attended high school with Milla Jovovich.
- Has one daughter with her husband Martyn LeNoble: Sadie Grace LeNoble (b. 1/27/11 at Cedars-Sinai Hospital in Los Angeles, CA).
- In August 2021, she revealed that she had been diagnosed with Multiple Sclerosis several months earlier.
- Grew up near the site of the notorious 1981 Wonderland (or Four-on-the-Floor) murders involving John Holmes. She later played Susan Launius, the sole survivor of the murders, in the movie Wonderland (2003).
- First appeared on television as an infant in a commercial for disposable diapers.
- Passed the GED with flying colors toward the end of her junior year.
- Last year, Applegate discussed how her life had been impacted since her M.S. diagnosis, explaining she had seen a 40lb weight gain and now struggles to walk without the support of a cane. -May 5, 2023.
- Is referenced in Donnie Darko (2001) by Jake Gyllenhaal's character while visiting the psychiatrist.
- Auditioned for the role of Samantha Micelli on Who's the Boss? (1984), which went to Alyssa Milano.
- Her love of the video-game Guitar Hero (2005) gave her a two-week migraine headache. She had to go to the doctor for treatment of the headache, taking time away from her television series. Has not played the game since 4/15/09.
- Was referenced in the song "Set Adrift on Memory Bliss" by the hip-hop group PM Dawn.
- Was hired by Jodie Foster to star as Paula Olsen in Nell (1994) but was dismissed after Foster was replaced by Michael Apted as director. Applegate was replaced by Natasha Richardson.
- Her mother wrote a song for her. She also sang the song, called "Christina's World".
- In October 2017, she had ovaries and Fallopian tubes removed to prevent ovarian cancer.
- Married longtime boyfriend Johnathon Schaech on 10/20/01, in a small Palm Springs (CA) ceremony, attended by immediate family and friends.
- Returned to work four months after giving birth to daughter Sadie in order to begin filming Up All Night (2011).
- Her personal manager for over 26 years was Tami Lynn, who was also her co-producing partner on her sitcom Jesse (1998).
- Has three cats and a turtle named Tibbell.
- Daughter of Robert Applegate and Nancy Priddy. Her ancestry includes English, Scottish, German, Irish, Scots-Irish (Northern Irish), Welsh, Dutch, French, Danish, Swedish, and remote Norwegian.
- Paid tribute to the late Elizabeth Taylor via Twitter, stating that Taylor's film Who's Afraid of Virginia Woolf? (1966) is her favorite movie and Taylor's portrayal of Martha her favorite movie performance (3/23/11).
- Finds Al Green's song "Simply Beautiful" one of the sexiest songs she has ever heard.
- Nominated in the Outstanding Actress in a Comedy Series, Up All Night (2011), at The Women's Image Network (WIN) Awards 2012.
- Supports People for the Ethical Treatment of Animals (PETA).
- She is one of four actors from Hall Pass (2011) to become a first-time parent the same year the film was released, along with her co-stars Owen Wilson, Jenna Fischer and Alyssa Milano.
- Chosen as one of People magazine's 100 Most Beautiful People in the World. (2009)
- Met her ex-husband, Johnathon Schaech, through director Gregg Araki.
- On 3/11/05, while on stage in Chicago in the Broadway-bound revival of the musical "Sweet Charity" (1966), she broke a bone in her right foot. On March 25, in Boston with Charlotte d'Amboise in the titular role, its producers officially canceled the production, announcing it would close after its last regularly scheduled tryout performance, the March 27 matinée. On March 29, the production was officially resurrected with a revised Broadway preview and opening schedule. Although Ms. d'Amboise continued in the lead role for the first week of Broadway previews, on April 18 Applegate made her Broadway debut as Charity Hope Valentine. On May 4, the second Broadway revival of "Sweet Charity" opened officially with Applegate as its star. She was nominated for a 2005 Tony Award for Best Actress in a Musical.
- In an interview on Late Night with Conan O'Brien (1993), she mentioned that though she has green eyes on one magazine cover picture, her eyes were changed to blue.
- Chosen as one of People magazine's 50 Most Beautiful People in the World. (1999)
- Became engaged to Martyn LeNoble, having been in a relationship with him since July 2008, after he proposed to her on a beach in Palm Springs, CA, on 2/14/10.
- Has one half-brother and one half-sister from subsequent marriage of her father, Robert Applegate, after he and Christina's mother, Nancy Priddy, divorced.
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