While it's an enjoyable character piece, it also excels at finding humor in a realistic topic that is extremely depressing. Face it. Cancer is a bitch. This movie attacks that topic head on and does so with extreme taste and a human touch that absolutely tugs at the heart. 50/50 makes it's point without ever being heavy handed or psychologically draining.
In the past I've given Rogen a really hard time about his lack of talent and often annoying habits on screen. This time I'm going to give him some credit. He actually has depth in this movie and exceeds his typical comic roles. Maybe he's finally maturing as an actor. Levitt has been one of my favorites for a while and I'm sure this movie with propel him to new status as one of today's shining stars. This man has quite a career in front of him and I cannot wait to see what he does next. Huston appeared to be recreating her role from The Darjeeling Limited. She's does a fair job with the material but just seems bland. Kendrick is another stand out in this film.
While the heavy topic of the film may not be for everyone, I would suggest giving it a chance. It's a realistic comedy that gracefully attacks a current topic while maintaining a strong sense of friendship, family, and the support system we would all need in a period of dwindling health.