While many patients with early-stage colon cancer are cured with surgery alone, the standard of care remains a uniform approach to adjuvant chemotherapy based primarily on tumor stage. Recently, increasing awareness of the need for more individualized decision-making in cancer care has led to the development of several potential prognostic and predictive markers in colon cancer. While adjuvant chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin is clearly beneficial to patients with stage III disease, well-validated molecular markers might help define which patients with stage II disease are likely to benefit from adjuvant therapy as well. Here, we review the data on the clinical development of molecular markers to individualize adjuvant therapy in colon cancer.