- John is a wonderful singer who came out of a musical theater background. He did all of his own singing in Chicago (2002).
- He met his wife in Thailand while he was filming Vittime di guerra (1989), who, at the time, was Sean Penn's assistant.
- In April 2004, he left the filming of Manderlay (2005) to be replaced by Slovenian actor Zeljko Ivanek. According to a report in Entertainment Weekly, he did so to protest against the killing of a donkey during production.
- For not only his broad, almost 6' 2" frame, curly hair, and everyman's mug, but also his straight-forward but thoughtful acting style, Reilly has frequently been dubbed "his generation's Gene Hackman".
- In 2003, he starred in three out of the five movies nominated for Best Picture. They are Chicago (2002), Gangs of New York (2002), and The Hours (2002). All of these films were produced by Miramax Films.
- His first plane ride was to Thailand to film Vittime di guerra (1989).
- Made a home video of himself singing in a bow tie and suit for director Rob Marshall who gave him his role in Chicago (2002).
- Received a Bachelor of Fine Arts degree from DePaul University's Goodman School of Drama (Chicago) (1987)
- Graduated from Brother Rice High School on the South Side of Chicago.
- As of 2021, has appeared in five films that were nominated for the Best Picture Oscar: La sottile linea rossa (1998), Chicago (2002), The Hours (2002), Gangs of New York (2002) and The Aviator (2004). Of those, Chicago (2002) is a winner in the category.
- Is a Chicago White Sox fan.
- Appeared in five films along Sean Penn: Vittime di guerra (1989), Non siamo angeli (1989), Stato di grazia (1990), La sottile linea rossa (1998) and Licorice Pizza (2021).
- Friends with Will Ferrell.
- Attended DePaul University in Chicago.
- Has frequently played a naive husband, oblivious to his wife's resentment of him, in Chicago (2002), The Hours (2002) and ...e ora parliamo di Kevin (2011).
- Was nominated for Broadway's 2000 Tony Award as Best Actor (Play) for a revival of Sam Shepard's "True West."
- Originated the role of Marty in the 2002 musical "Marty" (book by Rupert Holmes, music by Charles Strouse, lyrics by Lee Adams), based on the 1955 movie Marty - Vita di un timido (1955).
- Director Antoine Fuqua wanted to cast him in his since aborted crime epic "Tru Blu" with Denzel Washington and Benicio Del Toro.
- Lost a few pounds to play the rock star title character in Walk Hard - La storia di Dewey Cox (2007).
- Was member of the dramatic jury at the Sundance Film Festival in 2005.
- Will play the iconic role of Stanley Kowalski in the Roundabout Theatre Company's revival of Tennessee Williams' "A Streetcar Named Desire". (marzo 2005)
- Was considered for the role of Frank in Il grande e potente Oz (2013).
- John's father's ancestry was three quarters Irish, one eighth German, one sixteenth French-Canadian, and one sixteenth Scottish. John's maternal grandparents, Clemens Petronis and Veronica Strelciunas, were Lithuanian. He is the fifth of six children.
- Nominated for the 2019 Golden Globe Award in the Best Performance by an Actor in a Motion Picture - Musical or Comedy category for his role as Oliver Hardy in Stanlio & Ollio (2018), but lost to Christian Bale for Vice - L'uomo nell'ombra (2018).
- In addition to having worked with Leonardo DiCaprio in The Aviator (2004), he has also worked with two other actors who played Howard Hughes: Jason Robards (from Una volta ho incontrato un miliardario (1980)) in Magnolia (1999), and Tommy Lee Jones (from The Amazing Howard Hughes (1977)) in Radio America (2006).
- In the tradition of Alan Young's Filby from L'uomo che visse nel futuro (1960), Reilly plays a teenager aged 14 in his forties - aged 41, for Walk Hard - La storia di Dewey Cox (2007).
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