This review was performed to determine the efficacy of commonly used cytotoxic agents in the management of anthracycline-resistant breast cancer, using a stringent and uniform definition of drug resistance. We reviewed the reports of second- and third-line chemotherapy after anthracycline-containing regimens published over the last two decades. Only studies with sufficient information on the timing of progressive disease in relation to anthracycline therapy were considered. All assessable studies were reviewed individually, and the data obtained with taxanes in anthracycline-resistant breast cancer were also pooled to estimate the activity. The great majority of published studies on second- and third-line chemotherapy lack useful information about anthracycline resistance. Among the few studies with sufficient information about anthracycline resistance, several definitions were used. We reanalyzed those reports utilizing a uniform definition of anthracycline resistance: progression while receiving an anthracycline. Only studies using paclitaxel or docetaxel reported an activity in this anthracycline-resistant population, allowing a response rate between 6-50% and 32-57% for both agents respectively. The activity of other cytotoxic agents in anthracycline-resistant breast cancer could not be determined because a lack of accurate data using the stringent definition. Both paclitaxel and docetaxel have substantial antitumor activity in patients with clearly defined anthracycline-resistant breast cancer. The activity of other cytotoxic agents in this group of patients remains to be established.