Meg Ryan
as Kathleen Kelly

Tom Hanks
as Joe Fox

Greg Kinnear
as Frank Navasky

Heather Burns
as Christina Plutzker

Parker Posey
as Patricia Eden

Dave Chappelle
as Kevin Jackson

Jean Stapleton
as Birdie Conrad

Steve Zahn
as George Pappas

Dabney Coleman
as Nelson Fox

John Randolph
as Schulyer Fox

Hallee Hirsh
as Annabelle Fox

Jeffrey Scaperrotta
as Matt Fox

Cara Seymour
as Gillian Quinn

Katie Finneran
as Maureen, the Nanny

Michael Badalucco
as Charlie

Deborah Rush
as Veronica Cash

Veanne Cox
as Miranda Margulies

Bruce Jay Friedman
as Vince Mancini

Sara Ramirez
as Rose, Zabars Cashier

Howard Spiegel
as Henry, Zabars Shopper

Diane Sokolow
as Zabars Shopper

Julie Kass
as Zabars Shopper

Reiko Aylesworth
as Thanksgiving Guest

Katie Sagona
as Young Kathleen Kelly

Kathryn Meisle
as Cecilia Kelly

Nina Zoie Lam
as T.V. Reporter

Maggie Murphy
as Theater Patron

Michelle Blakely
as Shopper

Meredith White
as Shopper

Dianne Dreyer
as Shopper

Julie Galdieri
as Shopper

Leila Nichols
as Shopper

Mary A. Kelly
as Fox Books Shopper

Chris Messina
as Fox Salesperson

Ronobir Lahiri
as Man at Cafe Lalo

André Sogliuzzo
as Waiter at Lalo

Peter A. Mian
as Capeman

Richard Cohen
as Starbucks Customer

Enzo Angileri
as Starbucks Customer

Nick Brown
as Juggler

Ann Fleuchaus
as Sarah Mancini

Neil Bonin
as Party Guest

Bill McHugh
as Party Guest

Santiago Quinones
as Decorator

Lynn Grossman
as Yvette Fox

Dolores Sirianni
as Mother of Twins

Nicole Bernadette
as Florist

Jane Adams
as Sydney Anne (uncredited)

Cecelia Antoinette
as Restaurant Patron (uncredited)

Elwood Edwards
as Online 'You've Got Mail' Voice (voice) (uncredited)

Alfonso Gomez-Rejon
as Party Guest (uncredited)

Gideon Jacobs
as Young Joe Fox (uncredited)

Brick Mason
as Man Letting Joe Fox in (uncredited)

Scott Mullin
as Male Runner (uncredited)

Logan Steinhardt
as Kid in Bookstore (uncredited)

Anthony Welch
as Business Executive (uncredited)