Clinical trial data indicate that epirubicin-based adjuvant treatment of breast cancer is associated with marked improvement in relapse-free and overall survival compared with traditional cyclophosphamide/methotrexate/5-fluorouracil. The outcomes are comparable to those achieved with sequential use of doxorubicin/cyclophosphamide and paclitaxel. Dose intensification of epirubicin is feasible, with tolerable side effects and no increased risk of cardiotoxicity beyond that expected. Clinical trial data coupled with pharmacokinetic evidence provide a strong foundation and rationale for current and future investigation of epirubicin in combination with the taxanes in the adjuvant setting. An ongoing German study is evaluating epirubicin/cyclophosphamide in combination with trastuzumab as first-line therapy of metastatic breast cancer in patients whose tumors overexpress HER2/neu protein. These results, particularly the tolerability of this regimen, will form the basis for future adjuvant and neoadjuvant studies of epirubicin/trastuzumab-based regimens.