Gastric cancer is the second most frequently diagnosed malignancy worldwide, and the risk of relapse remains high in the majority of patients undergoing resection. Attempts to reduce this risk and prolong survival have led to numerous adjuvant chemotherapy trials that either had no benefit for patients or occasionally had controversial results. The recently reported Intergroup 0116 trial shows conclusive evidence of survival benefit for patients treated with postoperative chemoradiotherapy. In this Intergroup trial, which involves over 600 patients, a regimen of postoperative chemotherapy plus chemoradiotherapy was shown to prolong overall and disease-free survival in gastric cancer patients with stage IB through IV disease following a curative (R0) resection. This approach should be considered the standard of care in patients with gastric cancer who have undergone curative resection. Preoperative chemotherapy shows promise in downstaging tumors and increasing the rate of curative resection, but randomized trials are needed to assess survival benefits. Efforts to combine existing treatment modalities and new agents with novel mechanisms of action hold promise for the future.