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Gleeson was born in Dublin, Ireland. Graduating from University College Dublin, he worked for several years as a secondary school teacher in Belcamp College, in North County Dublin. Gleeson resides in Malahide, Co. Dublin. He and his wife, Mary, have been married since 1982 and have four sons, Domhnall (who appears in Harry Potter and the Deathly Hallows as Bill Weasley), Fergus, Brian and Ruari. Brendan is also a very talented fiddle player. He is good friends with fellow Irish actors Liam Neeson, Stephen Rea and Cillian Murphy.
Gleeson started acting at age 34 and has acted in more than 30 films including Braveheart, I Went Down, Michael Collins, Gangs of New York, Cold Mountain, 28 Days Later, Troy, Kingdom of Heaven, and The Village. He frequently appears in the role of mentor or authority figure; he played Hogwarts professor Mad-Eye Moody in the fourth and fifth Harry Potter films, Harry Potter and the Goblet of Fire and Harry Potter and the Order of the Phoenix. Gleeson won critical acclaim for playing Irish gangster Martin Cahill in John Boorman's The General in 1998.
He starred in the short film Six-Shooter in 2006, which won an Academy Award for best Live Action Short. In 2008, he starred in the Oscar-nominated film In Bruges with fellow Harry Potter actors Ralph Fiennes, Ciaran Hinds and Clémence Poésy.
In 2009, Gleeson won an Emmy Award for his portrayal of Sir Winston Churchill in Into the Storm.
- Smurfs 2 (2013)
- Safe House (2012)
- The Raven (2012) - Colonel Hamilton
- Harry Potter and the Deathly Hallows: Part 1 (2010) - Mad-Eye Moody
- Into the Storm (2009) - Sir Winston Churchill
- In Bruges (2008)
- Beowulf (2007)
- Harry Potter and the Order of the Phoenix (2007) - Mad-Eye Moody
- Studs (2006)
- Six-Shooter (2006 short)
- The Tiger's Tail (2006)
- Black Irish (2006) - Desmond
- Harry Potter and the Goblet of Fire (2005) - Barty Crouch Jr's Mad-Eye Moody disguise, Mad-Eye Moody
- Kingdom of Heaven (2005) - Raynald of Chatillon
- The Village (2004) - August Nicholson
- Troy (2004) - Menelaus
- Cold Mountain (2003) - Stobrod Thewes
- Dark Blue (2002) - Jack Van Meter
- Gangs of New York (2002) - Walter 'Monk' McGinn
- 28 Days Later (2002) - Frank
- Cáca Milis (2001) - The blind man
- Artificial Intelligence: AI (2001) - Lord Johnson-Johnson
- The Tailor of Panama (2001) - Michelangelo 'Mickie' Abraxas
- Mission Impossible II (2000) - John C. McCloy
- Harrison's Flowers (2000) - Marc Stevenson
- Lake Placid (1999) - Sheriff Hank Keough
- This Is My Father (1998) - Garda Jim
- The General (1998) - Martin Cahill
- I Went Down (1997) - Bunny Kelly
- Michael Collins (1996) - Liam Tobin
- Braveheart (1995) - Hamish Campbell
- Into the West (1992) - Inspector Bolger
- Far and Away (1992) - Social Club Policeman
- The Field (1990) - Quarryman
- The Treaty (1990) - Michael Collins