Given the single-agent activity of docetaxel and doxorubicin in metastatic breast cancer and their potential non-cross-resistance, several phase I/II pilot studies of either docetaxel/doxorubicin (TA) or TA plus cyclophosphamide (TAC) were conducted. The results of these studies show that the main toxicity is related to neutropenia and its consequences, although documented infections are rarely reported. Other toxicities are mild, while docetaxel-specific toxicities (fluid retention, nail changes, etc) are seldom seen. No significant cardiotoxicity, even when patients are exposed to a cumulative doxorubicin dose greater than 360 mg/m2, has been observed. In terms of efficacy, response rates in the range of 70% to 80% were noted in all studies, even for patients with visceral metastases. Preliminary data suggest that the combination of docetaxel with epirubicin is also feasible, with manageable toxicities and significant activity. Several phase III randomized trials using TA or TAC are presently being performed in first-line metastatic breast cancer and, most importantly, in the adjuvant setting to assess whether TA-based combinations will change the natural history of breast cancer.