Despite recent progress in our knowledge about the development and therapy of colorectal cancer (CRC), it still remains one of the major cancer related deaths throughout the world. With the introduction of new cytotoxic and targeting agents a significant improvement in progression-free and overall survival has been achieved. However, a significant percentage (40-50%) of patients do not experience beneficial effects and suffer from severe toxicities. It will be critical to identify molecular markers, which may help to assess therapeutic response and outcome in CRC. Validation of predictive and prognostic molecular markers will enable oncologists to tailor patient specific treatment strategies for the individual patient according to the molecular profile of both the patient and their tumor. Individualized therapy will help to improve therapeutic efficacy and to minimize toxicities and therapeutic expenses.