- Robin Williams - Dr. Eddy
- Rhea Perlman - Mittens
- Jane Kaczmarek - Beth
- John Michael Higgins - Dr. Cahill
- Damon Herriman - Jesse
- Duncan Bravo - Cop
- Nikki Hahn - Little Girl
- Rashida Jones - Lisa
- Irene Choi - Young Woman
- Richard Denni - Mr. Gordon
- Roger V. Burton - Patient #1
- Gwen Van Dam - Patient #2
- Tom Virtue - Doctor
- Gibson Bobby Sjobeck - Tyler
- Jeff Holman - Delivery Man
- Jared Gilmore - Young Ryan
- Diane Robin - Mother
- Peter Stormare - Trashface
- George Coe - Gene
- Wayne Wilderson - Charlie
- Sally Brooks - Mrs. Stevenson
- Maxim Knight - Adam
- Chad Morgan - Maddie
- Dwight Yoakam - Bruce
- Katy Mixon - Angelique
- Gabriella Pession - Cinzia
- Charles Esten - Nick
- E.J. Callahan - Mr. Helms
- Chip Chinery - Stanley
- Kari Coleman - Suzy
- Kyle Davis - Budtender
- Ellia English - Ruby
- Tom Yi - Cal Fukazaki
- Ray Wise - Colt St. Cloud
- Keegan-Michael Key - Dick Barbian
- J.P. Manoux - Leo
- Ethan Suplee - Spencer
- Rodney To - Dr. Bangachon
- Danielle Reierson - Insurance Rep
- Rachel Sterling - Waitress
- Katherine Disque - Mother
- Alejandra Janet Varela Jiménez - Sarah
- Al Sapienza - Poochy Poochy Guy
- Matt Kaminsky - Vet Tech
- Nestor Carbonell - Dr. Arturo Ramos
- Zachary Knighton - Bill
- Gina Gershon - Gloria
- Barry Watson - Michael McDerry
- Gerry Bednob - Mr. Patel
- Leonard Robinson - Andre
- K.T. Thangavelu - Mrs. Patel
- Randee Heller - Margot
- Kyle Mooney - Alan
- Roderick McCarthy - Cop
- Mary Steenburgen - Catherine Newman
- James Remar - Henry Newman
- Kristen Schaal - Anne
- Jim Jansen - Older Man
- Claire Titelman - Dog Walker
- Tommy Dickie - Co-worker
- Candi Milo - Secretary
- Elana Staehli
Peter Stormare hace el papel de Trashface.
Ethan Suplee interpreta a Spencer en la serie.
Robin Williams interpreta a Dr. Eddy en la serie.
Mary Steenburgen hace el papel de Catherine Newman.
James Remar interpreta a Henry Newman en la serie.
Elijah Wood hace el papel de Ryan Newman.
Jason Gann hace el papel de Wilfred.
Fiona Gubelmann hace el papel de Jenna Mueller.
Dorian Brown Pham interpreta a Kristen Newman en la serie.
Chris Klein interpreta a Drew en la serie.
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