The role of adjuvant chemotherapy in patients with stage III resected colon cancer is currently well established. Current treatment options for stage III colon cancer include oxaliplatin-based/5-fluorouracil/leucovorin combination chemotherapy, or fluoropyrimidine monotherapy with 5FU/leucovorin or capecitabine, depending on the assessed risk-benefit ratio from combination treatment in each patient. In fact, the addition of oxaliplatin to 5FU has been shown to be beneficial, although the improvement in disease-free survival comes at a cost of increased risk of treatment-related morbidity. The benefit of adjuvant chemotherapy has been harder to demonstrate in other subgroups of patients, notably those with stage II colon cancer and those with rectal primaries. The addition of targeted agents, such as monoclonal antibodies cetuximab, panitumumab, and bevacizumab, to chemotherapy in the adjuvant setting is appealing and is the subject of ongoing trials. Another significant ongoing research interest is the identification of better prognostic and predictive tools than the current staging methods used.This review will summarize the development of adjuvant chemotherapy in colorectal cancer, discussing particular topical issues related to its use.