Gastric adenocarcinoma is the most common malignancy of the upper gastrointestinal tract. During the past two decades it has migrated toward the gastroesophageal junction. Gastroesophageal reflux and obesity may play a role. Recent research suggests that a number of biologic and molecular differences exist in patients with gastric cancer. Further investigation in these areas may help in predicting outcome and directing therapy. Gastric cancer is not a curable condition when metastases are present. However, postoperative chemotherapy plus chemoradiotherapy, in the Intergroup trial 0116, prolonged the overall and disease-free survival rates of patients after a curative (R0) resection. It should be considered the new standard of care in patients with gastric cancer who have undergone curative resection with stage Ib-IV disease. Preoperative therapy strategies may increase the likelihood of R0 resection and remain an area of active investigation. Finally, development of more active agents is needed for the treatment of metastatic tumors.