Despite a marked decline in the incidence of gastric carcinoma in Western countries, the majority of patients presents with advanced inoperable tumors. In this setting, usually the aim of therapy is palliation, with the exception of chemotherapy administered in the attempt to downstage the tumor and to facilitate potentially curative surgery in patients with locally advanced nonmetastatic disease. This review will focus on the use of chemotherapy for advanced gastric cancer and after curative surgery, providing an overview of future directions for clinical research: preoperative (neoadjuvant) systemic chemotherapy, intraperitoneal treatment, and newer drugs.