- Steven Pasquale - Sean Garrity
- Diane Farr - Laura Miles
- Callie Thorne - Sheila Keefe
- Dean Winters - Johnny Gavin
- Larenz Tate - Bart 'Black Shawn' Johnston
- Larenz Tate - Bart Johnston
- James McCaffrey - James 'Jimmy' Keefe
- James McCaffrey - Jimmy Keefe
- Kaitlin Hopkins - Jennifer's Mom
- James Badge Dale - Timothy Gavin
- Bryan Batt - Photographer #1
- Taylor Dayne - Shirley
- Siobhan Fallon Hogan - Phyllis
- Holter Graham - Bartender
- John Salley - Tall Guy
- Julie White - Dr. Goldberg
- Brian McNamara - Passing Fireman
- Deanne Bray - RoseMary
- Alison Bartlett - Deb Stackhouse
- Jessica Leccia - Mary Magdalene
- Timothy Adams - Mike's Roommate
- Manny Perez - Luis
- Matthew Arkin - Dr. Thompkins
- Noelle Beck - Mariel
- Alexa Havins - Talker
- Kristina Apgar - Nicole
- Kate Burton - Rose
- David Vadim - Paulie
- Curtiss Cook - Project Resident
- Susan Misner - Theresa
- Charles Durning - Michael Gavin
- Charles Durning - Tommy's Dad
- Jennifer Ferrin - Sara
- Patricia Velásquez - Nez
- Phil Esposito - Chief Izzy
- Ashlie Atkinson - Theresa
- John Rothman - Bud
- Sherri Saum - Natalie
- Ramón Rodríguez - Kevin Vasquez
- Marisa Tomei - Angie
- James Biberi - Vinny
- Bruce Altman - Dr. Shinsky
- Lenny Clarke - Uncle Teddy
- Artie Lange - Mike Shea
- Milena Govich - Candy
- Jarah Mariano - Jarah
- Lyndon Byers - Ryan
- Peter Maloney - Uncle Red
- Kristina Klebe - Mickey's Girlfriend
- Gerry Bamman - Doctor
- Neal Jones - Peter
- Anthony Alessandro - Sebastian
- Paula Devicq - Sondra
- Lee Tergesen - Sully
- Patti D'Arbanville - Ellie
- Cynthia Harris - Mike's Mom
- Robert Turano - S.I. Chief
- Susan Sarandon - Alicia Green
- Tony Cucci - Sal
- Chris Bowers - Larry Bird
- Karen Goberman - Franco's Nurse
- Judy Del Giudice - Italian Woman
- Jill Latiano Howerton - Geneva
- Michael Mulheren - Chief Perolli
- Kevin Hagan - Captain Sweeney
- Greg D'Agostino - NYPD Officer (uncredited)
- Greg D'Agostino - NYPD Officer
- Chester A. Sims II - Mr. Wilmore
- Natalie Distler - Colleen Gavin
- Trevor Heins - Connor Gavin
- Olivia Crocicchia - Katy Gavin
- Jay Potter - Roger Mills
- Virginia Louise Smith - Lisa
- James Colby - Joey the Third
- Paige Turco - Nell Turbody
- Hunter Reid - Johny Gavin at 5
- Rosemarie DeWitt - Heather
- John Speredakos - Jewish Cop
- Harriett D. Foy - Karlene Simpson
- H. Jon Benjamin - Gary
- Robert John Burke - Mickey Gavin
- Bernardo de Paula - Jesus Christ
- Christopher Durham - Father Murphy
- Anthony Mangano - Bobby Vincent
- Anthony Mangano - Bobby
- Cam Neely - Mungo
- Marie-Line Grinda - Dr. Collins
- Michael J. Fox - Dwight
- Michael Zegen - Damien Keefe
- Ned Eisenberg - Burt
- Jennifer Esposito - Nona
- Desmond Harrington - Troy
- James Hindman - Insurance Guy
- Chance Kelly - Jimmy the Jew
- Cornell Womack - Richard
- Joe Remy Dolinsky - Waiter (uncredited)
- Lauren Hines - Court Reporter (uncredited)
- Michael Masucci - Sports Fan (uncredited)
- Lesley Shires - Girl in Cafe (uncredited)
- Vincent Piazza - Tony
- Alanna Thompson - Bartender (uncredited)
- Jerry Adler - Sidney Feinberg
- Peter Conboy - New York City Police Officer
- Jason A. Drago - Emergency Medical Technician
- Kyle Hughes - Firefighter Burns
- Wayne Scott Miller - Basketball Coach
- Andrew George Jr. - Johnny Gavin at 12
- Gerald Bunsen - Spanish Guy #1
- George Deihl Jr. - Cell Phone Guy #2
- Gina Gershon - Valerie
- Bridget Moloney - Texter #2
- James Lloyd Reynolds - Date
- Amy Sedaris - Beth
- Natalie Williams - Christina
- Anthony Perullo - Derek
- Richard Thomsen - Max
- David Call - Young Man / Connor
- David Call - Connor
- Lamar Brown - Bar Patron (uncredited)
- Kevin Chapman - Terrance
- Kathleen Chalfant - Sean's Ma
- Tawny Cypress - Carla
- Joel de la Fuente - Dr. Lee
- Regan Mizrahi - Timmy
- Betsy Aidem - Doctor
- Lisann Valentin - Patron (uncredited)
- Peggy J. Scott - Jeannie Reilly
- Myk Watford - Steve
- Brette Taylor - Debbie
- Mark Mineart - Man on Ledge
- Julienne Hanzelka Kim - Doctor
- Christopher McHale - Middle Aged Man
- Stephen Beach - Detective
- Tammy Morris - Karen
- Thomas Lyons - Connor's Killer
- Frank Anello - Angry Cop
- Brian Delate - Priest
- Jennifer Sciole - Female NYPD Officer (uncredited)
- Sonny Vellozzi - Train Commuter (uncredited)
- Denis Leary
- Peter Tolan
Marisa Tomei interpreta a Angie en la serie.
Denis Leary interpreta a Tommy Gavin en la serie.
Neal Jones interpreta a Peter en la serie.
Charles Durning interpreta a Michael Gavin en la serie.
Susan Sarandon interpreta a Alicia Green en la serie.
Curtiss Cook interpreta a Project Resident en la serie.
Adam Ferrara interpreta a Chief 'Needles' Nelson en la serie.
Andrea Roth interpreta a Janet Gavin en la serie.
John Scurti hace el papel de Kenneth 'Lou' Shea.
Daniel Sunjata hace el papel de Franco Rivera.
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