Adjuvant therapy in colorectal cancer has always been a controversy during years. Despite the fact that benefit of adjuvant therapy in stage III is clear, a more controversial question concerns efficacy in stage II. The introduction of new drugs in addition to standard regimens has some benefit, but also adds toxicity. Ongoing studies with novel targeted therapies will show their results in the next years. Other open questions include duration of therapy and whether there is a real possibility of selecting patients for treatment on the basis of prognostic factors.