At present, standard adjuvant treatment for patients with stage III colon cancer after surgical resection is represented by 6 months of chemotherapy based on 5-fluorouracil/leucovorin regimens. Even elderly patients enjoy the benefit of chemotherapy in terms of superior overall survival with no detrimental effects on quality of life. More questionable is the role of adjuvant chemotherapy for stage II colon cancer patients, the standard of care for whom is surgical resection alone. Although a majority of patients will be cured with resection, a significant minority will ultimately relapse, suggesting the need to identify patients who may benefit from adjuvant therapy. Putative prognostic markers for stage II patients, as well as the state-of-the-art of the adjuvant treatment in this setting, are reviewed in this paper.