Gastric cancer remains one of the most common forms of cancer worldwide. Unfortunately, most patients will present with advanced-stage disease, and will therefore need palliative chemotherapy. Some chemotherapy regimens have been well established as first-line therapy, and have been shown to increase survival; however, almost all patients with metastatic gastric cancer will develop progressive disease after first-line therapy. With the availability of several active chemotherapy drugs, many patients who retain a good performance status after the initial treatment remain good candidates for additional therapy; however, no standard approach for second-line therapy exists. Many small, phase 2 trials have been done and the findings are variable. No data from randomised-controlled trials suggest a benefit of second-line chemotherapy compared with supportive care alone. We review the published data concerning the use of chemotherapy in the second-line setting for the treatment of advanced gastric cancer.