Because of its frequency and mortality rate, colorectal cancer represents a major public health problem. Adjuvant chemotherapy has improved the prognosis. Six months of oxaliplatin and fluoropyrimidine in combination is the standard adjuvant treatment in stage III patients. Two monoclonal antibodies, bevacizumab targeting vascular endothelial growth factor and cetuximab targeting epidermal growth factor receptor 1, are being assessed in addition to chemotherapy in the adjuvant setting. Preliminary results of 2 trials have shown disappointing results. Duration of therapy is another other critical issue for the future. Adjuvant chemotherapy in patients with stage II colon cancer is still a subject of controversy. The potential biomarkers that can accurately select patients with stage II or III cancer who are at risk for recurrence to individualize therapy from microsatellite instability to gene signature are reviewed. Adjuvant therapy in elderly patients is another matter of debate due to the lack of survival advantage in the recent trials.