Although the incidence of gastric cancer has been declining in the United States, the disease continues to pose a devastating problem worldwide. Complete surgical resection offers the only chance of cure for localized gastric cancer. The recommended extent of surgical lymphadenectomy has been debated for some time, but no consensus has emerged. Unfortunately, local and distant recurrence are frequent, and long-term survival remains low. Randomized adjuvant chemotherapy trials have shown mixed results, with no consistent overall survival benefit. The Gastric Cancer Intergroup Trial 0116 demonstrated that adjuvant chemoradiotherapy with 5-fluorouracil/leucovorin significantly improves disease-free and overall survival. More recently, the MAGIC trial showed a survival benefit with perioperative chemotherapy. Preoperative (neoadjuvant) chemotherapy and chemoradiotherapy have also been explored in phase II studies, with encouraging results; however, the potential benefits of these approaches need to be assessed in phase III trials. Biologic agents are beginning to be incorporated into multimodality treatment and have shown promising results thus far.