Colorectal cancer is a leading cause of cancer-related mortality in the USA. Although recent years have brought significant advances in treatment in the metastatic setting, the last major advance in the adjuvant setting was the addition of oxaliplatin to fluorouracil and leucovorin in the treatment of stage III disease. The benefit of adjuvant therapy in patients with stage II disease is not as clear. Prognostic and predictive markers help stratify patient risk and thereby indentify patients who may benefit from adjuvant therapy. The goal of this review is to help define the prognostic markers and molecular predictors that should be considered when attempting to personalize adjuvant therapy.