Systemic treatments for patients with colon cancer has expanded broadly beyond 5-fluorouracil-based chemotherapy. For patients with early-stage colon cancer who are considering adjuvant chemotherapy, multiple factors such as the risk of disease recurrence, absolute survival benefit of chemotherapy, treatment toxicity, and patient comorbid medical conditions must be taken into account. In the metastatic setting, biomarkers such as KRAS/NRAS/BRAF mutation, microsatellite instability status, and left- versus right-sided colon cancer have helped oncologists to tailor systemic treatment regimens, which include chemotherapy, targeted therapy, and immunotherapy.