Adjuvant treatment should be considered in all patients with newly diagnosed resectable colon cancer stage II and III. Clinical and histopathological criteria are relevant for identifying patients who will most likely benefit from systemic treatment. Nowadays, defective mismatch repair or high microsatellite instability (MSI-H) should be tested before considering chemotherapy in stage II colon cancer. Targeted immune-oncologic therapies and predictive molecular markers, such as circulating tumor DNA (ctDNA), are currently being evaluated in clinical trials. The number of older patients with cancer will considerably increase over the next few years and will require greater attention in clinical trials and guidelines.