Survival rates for patients undergoing resection of gastric adenocarcinoma remain poor. Even following successful removal of all gross disease, high rates of local-regional and systemic recurrence are observed. During the past twenty-five years, multiple trials have been undertaken to evaluate the possible benefit of either preoperative or postoperative adjuvant chemotherapy in this disease. This report reviews the rationale, design, and outcome of these trials, and further updates the status of preoperative chemotherapy protocols currently employed at the M.D. Anderson Cancer Center.