Prior to 1974 gastric cancer was considered refractory to chemotherapy. Single agent 5-Fluorouracil, mitomycin, and the nitrosoureas produced modest response rates with no augmentation of survival as compared to historical controls. Combinations of these agents produced slight increases in survival. The addition of doxorubicin, which had no major impact as a single agent, to 5-Fluorouracil and mitomycin C in 1974 produced impressive response rates over 40%, although these early optimistic results were tempered in randomized multi-institutional trials. Nevertheless, median overall survivals appear to have increased with this regimen over historical controls, and the substitution of cisplatin or methyl-CCNU for mitomycin C in Phase II trials has produced equivalent results. Comparison with historical controls is problematic as it is unknown what role more aggressive surgery and supportive measures may have played in increasing survival. Encouraging results with combination therapy in advanced gastric cancer have suggested opportunities to employ combination chemotherapy as adjuvant therapy or together with radiation for locally advanced gastric cancer. The role of less cardiotoxic derivatives of doxorubicin remains to be more fully explored.