| Paul Rudd | Pete |
| Leslie Mann | Debbie |
| John Lithgow | Oliver |
| Megan Fox | Desi |
| Iris Apatow | Charlotte |
| Maude Apatow | Sadie |
| Chris O'Dowd | Ronnie |
| Jason Segel | Jason |
| Melissa McCarthy | Catherine |
| Graham Parker | Himself |
| Albert Brooks | Larry |
| Charlyne Yi | Jodi |
| Robert Smigel | Barry |
| Annie Mumolo | Barb |
| Lena Dunham | Cat |
More This Is 40 Pictures
After many years of marriage, Pete is the sole male in a household that includes his wife, Debbie, and two young daughters . As Pete struggles to keep his record label afloat, he and Debbie navigate a three-week course of sex and romance, career victories and financial hardships, aging parents and maturing children. They'll have to learn to forgive, forget and enjoy the rest of their lives -- before they kill each other.