Despite the recent decline in the incidence of gastric cancer in North America and Western Europe, treatment remains a challenging problem for oncologists. Surgery is the primary modality for managing early-stage disease, but most patients who undergo a curative resection develop locoregional or distant recurrence. Consequently, there has been great interest in evaluating strategies to prevent recurrences and improve overall mortality. This article is a review of data on adjuvant and neoadjuvant treatment approaches for gastric cancer, including radiotherapy, chemotherapy, and chemoradiotherapy. Compared with surgery alone, the North American Intergroup 0116 trial demonstrated a clear survival benefit with the administration of a postoperative regimen of 5-fluorouracil, leucovorin, and external beam radiation therapy, and these findings have made concurrent chemoradiation a standard of care in patients with resected gastric cancer. More recently, the British Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) study found that preoperative and postoperative administration of epirubicin, cisplatin, and 5-fluorouracil significantly improved survival beyond surgery alone. Thus, after decades of negative studies, 2 successful strategies in localized gastric cancer are now available. Ongoing and proposed trials include the current Intergroup study (Cancer and Leukemia Group B 80101), which is assessing the role of a potentially more active postoperative chemoradiation regimen. The proposed MAGIC-B study will examine the role of adding bevacizumab to perioperative chemotherapy, and the planned CRITICS study by the Dutch Gastric Cancer Group will evaluate the role of postoperative chemoradiation in combination with preoperative chemotherapy.