Salvage chemotherapy for metastatic breast cancer includes regimens for hormonal responsive patients and patients refractory to cyclophosphamide, methotrexate, and fluorouracil (CMF) or fluorouracil, doxorubicin, and cyclophosphamide (FAC). For hormone responsive patients, progestins, aminoglutethimide with hydrocortisone, and androgens provide second-line therapy and produce objective remissions in 50% of patients. Some patients respond to further hormonal manipulation. When metastatic disease becomes refractory, combination chemotherapy is the treatment of choice. For those patients refractory to CMF, salvage therapy should consist of single agents, such as mitomycin, doxorubicin, or vinblastine, or combinations of drugs not contained in the CMF regimen. As with single-agent therapy in previously untreated patients, remission durations are usually short. Two-drug combinations result in response rates from 30% to 50% and longer duration of remission. For patients refractory to FAC, doxorubicin is discontinued after reaching a cumulative dose, and therapy is continued with a CMF-type combination. Thus, both doxorubicin and methotrexate are used, and salvage chemotherapy is based on mitomycin and vinblastine. All agents used for salvage therapy of breast cancer may produce toxic effects. Appropriate surveillance and limiting the cumulative dose of drugs reduces the risk of irreversible toxic effects.