Historically, doxorubicin has been the most effective single agent in metastatic breast cancer, and the combination of doxorubicin with other active agents (as in the 5-fluorouracil/doxorubicin/cyclophosphamide protocol) has improved patient outcome. Results from phase II and several recent phase III studies provide evidence that new agents are also highly active in the treatment of metastatic breast cancer and suggest that they would be active in combination regimens with the anthracyclines. In particular, docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has achieved a significantly higher response rate than doxorubicin in phase III randomized clinical trials. Studies to date indicate that this high response rate is achieved without accompanying cardiotoxicity. Several other new agents, notably, paclitaxel, vinorelbine, and gemcitabine, also have been evaluated in combination with the anthracyclines.