- Huffman was among dozens charged by the FBI and U.S. Attorney's Office on March 12, 2019, in a nationwide college entrance exam cheating scandal. Prosecutors alleged that Huffman's $15,000 donation to the Key Worldwide Foundation, ostensibly a charitable contribution, was in fact payment to a person who pretended to be Huffman's daughter, took the SAT for her, and received a score greatly improved from the daughter's score on the Preliminary SAT (PSAT). Huffman was arrested on March 12, charged with conspiracy to commit mail fraud and honest services mail fraud, and released on $250,000 bail. At her court appearance in Boston on April 3, she acknowledged her rights, charges, and maximum possible penalties; she waived a pretrial hearing, signed conditions of her release, and was allowed to leave. On April 8, she agreed to plead guilty to one count of conspiracy to commit mail fraud and honest services mail fraud. Huffman formally pleaded guilty to honest services fraud on May 13, 2019, and on September 13 she was sentenced to 14 days in jail. Upon her release she will receive one year of supervised release. She was also fined $30,000 and ordered to undertake 250 hours of community service. On October 15, 2019, Huffman reported to the Federal Correctional Institution in Dublin, California, to begin her sentence. She was meant to be released from prison on October 27, 2019 but was released 2 days early because October 27 fell on a weekend.
- On September 6, 1997, she married her boyfriend of 15 years William H. Macy. They met when he taught drama at New York's Atlantic Theatre Company.
- On an episode of Oprah Winfrey's "Wildest Dreams" segments, Huffman's dream came true when she got to sing backup to her idol Tina Turner who was performing live for Oprah. (February 2005)
- She told Oprah Winfrey that when she was born, her mother named her "Flicka", but had to change it because it was not a Christian name. She still uses "Flicka" as a nickname. The name "Flicka" comes from the book and movie My Friend Flicka (1943), a childhood favorite about a frisky young colt. The name means "girl" in Swedish.
- She stated on Finding Your Roots with Henry Louis Gates, Jr. (2012) that, as a young teenager of thirteen or fourteen, she discovered that her biological father was Roger Tallman Maher, a family friend.
- Has six older sisters named Mariah, Betsy, Jane, Grace, Jessie and Isabel and an older brother named Moore Jr.
- Jessica Alba was one of her students at the Atlantic Theater Company.
- Graduated from the prestigious Interlochen Arts Academy in Interlochen, Michigan, where she majored in theater (1981).
- Grew up in Aspen, Colorado.
- Her parents divorced when she was one year old.
- Invited to join the Academy of Motion Picture Arts and Sciences (AMPAS) in 2006.
- One of her idols is Tina Turner.
- Mother, with her husband William H. Macy, of daughters Sofia Macy (Sofia Grace Macy) (b. August 1, 2000) and Georgia Macy (Georgia Grace Macy) (b. March 14, 2002).
- She was replaced by Diane Venora on the situation comedy Thunder Alley (1994).
- Was forced to turn down a role in Jean-Paul Salomé's The Chameleon (2010) because of scheduling conflicts with Desperate Housewives (2004).
- Friends with Sarah Paulson. They starred together on Path to War (2002), The D.A. (2004) and Desperate Housewives (2004) where they played sisters. Both also were on Law & Order (1990) but played in different episodes. They shared nomination for Golden Globe 2017 and Paulson won it.
- Shares a birthday with Desperate Housewives (2004) co-star Jesse Metcalfe.
- She has German, English, French, Scots-Irish/Northern Irish, Scottish, Dutch, and Irish ancestry. Among her prominent ancestors are her great-grandfathers, Gershom Moore Peters, founder of the Peters Cartridge Company and prominent Baptist minister, and Frederick Berthold Ewing, a prominent St. Louis businessman, and her great-great-grandfather, Joseph Warren King, who founded the King Mills Powder Company.
- Was among the guests at Marcia Cross' wedding to Tom Mahoney
- Sang backup for Rebecca Pidgeon's album "The New York Girls' Club" (1996).
- She is the daughter of Moore Peters Huffman and his then wife Grace Valle (née Ewing), she and her siblings were raised by both of their parents.
- She was awarded a Star on the Hollywood Walk of Fame for Television at 7060 Hollywood Boulevard in Hollywood, California on March 7, 2012.
- On March 1, 2012, she launched What The Flicka, a website dedicated to women and mothers where she is a regular contributor.
- Returned to work three months after giving birth to her daughter Sofia in order to begin filming her guest appearance on The West Wing (1999). Also returned to work five months after giving birth to her daughter Georgia in order to begin filming her guest appearance on Girls Club (2002).
- Childhood celebrity crush was Henry Winkler (as "The Fonz").
- Best friends with Patricia Wolff.
- Likes herbal tea.
- As of 2018, has never appeared in a Best Picture Oscar nominated film.
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