Etoposide has modest single-agent activity (21% partial response rate) in patients with previously untreated metastatic gastric carcinoma. The use of etoposide in combination with agents like doxorubicin, cisplatin, and 5-fluorouracil with or without leucovorin has been of increasing interest to oncologists. Such combinations have been reported to produce overall response rates as high as 60% to 70%, with complete response rates as high as 20%, in patients with advanced measurable gastric carcinoma. Etoposide-containing regimens have also been used preoperatively in potentially resectable patients. In these studies, approximately 60% of treated patients may be rendered disease-free following resection. Preoperative (neoadjuvant) therapy has not yet been shown in phase III studies to be superior to surgery alone. Significant myelosuppression is the major toxicity of etoposide-based chemotherapy. Such chemotherapy deserves further evaluation in the treatment of gastric cancer.