Gastric cancer is the fourth most commonly diagnosed cancer and is the second leading cause of cancer death worldwide. More than 50% of patients undergo surgery, but even after a curative resection, 60% of patients relapse locally or with distant metastases. Despite the fact that many advances have occurred in the management of gastric cancer, it continues to carry a poor prognosis, amplifying the importance of palliative chemotherapy. When compared with best supportive care alone, combination chemotherapy yields a significant advantage in the management of advanced gastric cancer. However, no single regimen has emerged or been accepted as clearly superior over another. Numerous phase II studies have demonstrated promising results with newer agents including irinotecan, docetaxel, capecitabine, S-1, and oxaliplatin. Recently reported phase III results with these agents now demonstrate positive developments in the treatment options for patients with advanced gastric cancer.