Tom Hanks ... Sam Baldwin
Meg Ryan ... Annie Reed
Ross Malinger ... Jonah Baldwin
Rita Wilson ... Suzy
Victor Garber ... Greg
Tom Riis Farrell ... Rob
Carey Lowell ... Maggie Baldwin
Bill Pullman ... Walter
Le Clanche du Rand ... Barbara Reed
Kevin O'Morrison ... Cliff Reed
David Hyde Pierce ... Dennis Reed
Valerie Wright ... Betsy Reed
Frances Conroy ... Irene Reed
Tom Tammi ... Harold Reed
Calvin Trillin ... Uncle Milton
Caroline Aaron ... Dr. Marcia Fieldstone (voice)
Linda Wallem ... Loretta
LaTanya Richardson Jackson ... Harriet (as LaTanya Richardson)
Rosie O'Donnell ... Becky
Tom McGowan ... Keith
Steve Mellor ... Wyatt (as Stephen Mellor)
Marguerite Schertle ... Baltimore Waitress
Dana Ivey ... Claire
Brian McConnachie ... Bob
Rob Reiner ... Jay
Gaby Hoffmann ... Jessica
Matt Smith ... Mailman
Amanda Maher ... Clarise
Barbara Garrick ... Victoria
Victor Morris ... Seattle Maitre D'
Philip Mihalski ... Seattle Waiter
Donald J. Lee Jr. ... Seattle Detective
Mary A. Kelly ... Nervous Woman on Airplane
Diane Sokolow ... Tiffany Saleswoman
Hannah Cox ... Jessica's Mother
Rich Hawkins ... Jessica's Father
Tamara Plank ... Stewardess (as Tamera Plank)
Michael Badalucco ... New York Taxi Dispatcher (as Mike Badalucco)
Jeff Mazzola ... New York Taxi Dispatcher
Philip Levy ... Taxi Driver
Julie Janney ... Cynthia
Tony Zazula ... Maitre D'
John Boylan ... Elevator Man
Robert Livingston ... Elevator Man
Butch Stevenson ... Valet
Sidney Armus ... Information Booth Man