The use of adjuvant chemotherapy for stage II colon cancer remains controversial. The accurate assessment of the risk factors associated with recurrence in patients with stage II disease is the key to identifying the patients that are most likely to benefit from adjuvant chemotherapy. Recent guidelines advocate that adjuvant chemotherapy for high-risk stage II colon cancer should take into account factors such as the T stage, number of lymph nodes examined, tumor differentiation, and tumor perforation. In addition to these clinicopathological factors, there has also been intense interest in the identification of new prognostic or predictive biomarkers that can improve outcomes through better patient classification and selection for adjuvant chemotherapy. Recent advances in the field of molecular genetics have led to the identification of specific biomarkers involved in colorectal cancer progression, whereas gene expression microarray technology has led to the identification of molecular profiles able to predict recurrence or benefit from adjuvant chemotherapy. However, none of these has yet been validated in large prospective clinical trials. In this article, we review the current status of prognostic and predictive biomarkers for stage II colon cancer and provide an update on the most recent developments.