Gastric cancer is a very challenging malignancy given that it presents late, has complex pathogenetic mechanisms with multiple carcinogenic processes implicated, and is only moderately sensitive to chemotherapy and radiation. Accurate staging for gastric cancer is possible with the availability of sophisticated imaging studies, endoscopic ultrasound, and laparoscopy. Postoperative chemoradiation is the standard of care in high-risk patients with resected primary disease. Recent encouraging results with the preoperative approach need to be studied further and prospectively compared to postoperative chemoradiation. Chemotherapy has yielded better results than best supportive care for metastatic gastric cancer and also improves quality of life, although all of these studies included a small number of patients. The last decade has seen newer agents used alone or in combination, with promising results. We anticipate that improved trial design, availability of molecular techniques, and continued search for better cytotoxic and targeted agents will help develop better treatments for patients with advanced gastric cancer.