The use of high-dose chemotherapy with stem-cell rescue (HDC-SCR) in the treatment of breast cancer is reviewed. The rationale for HDC-SCR in breast cancer is based on the principles of dose response and dose intensity. After conventional-dose chemotherapy, hematopoietic progenitor cells are harvested from the bone marrow or peripheral blood. The patient then undergoes HDC-SCR. Peripheral-blood progenitor cells are becoming the preferred cells for hematopoietic rescue. Most clinical trails of HDC-SCR in metastatic breast cancer have resulted in high overall objective response rates (57-100%), with the highest rates occurring in patients with minimal residual disease or chemotherapy-sensitive disease at the time of high-dose treatment. Most protocols now include induction therapy before HDC-SCR; only patients who show sensitive disease proceed to high-dose therapy. In most studies published to date, the median duration of remission was less than one year from the time of high-dose therapy; however, 10-15% of patients achieved complete remissions lasting two or more years. Most patients relapse, however. Some studies have suggested value of HDC-SCR as consolidation therapy in the adjuvant setting for women at high risk of relapse. Short-term toxicities of HDC-SCR are manageable in experienced hands. Notable long-term adverse effects include leukemia, sterility, pulmonary toxicity, and hemolytic uremic syndrome. Unresolved issues include the utility of purging occult cancer cells from stem-cell-bearing specimens, the best preparative regimen, the implications of autologous graft-versus-host disease, the use of sequential cycles of high-dose chemotherapy, cost-effectiveness, and effectiveness compared with standard therapy. HDC-SCR appears to be a valid option for selected patients with metastatic breast cancer, and in the adjuvant setting for patients at high risk of recurrence. The cost-benefit profile remains to be defined in randomized trials.