The treatment of breast cancer has progressed substantially over the past 15 years. Data from randomized adjuvant trials have shown that the risk of disease recurrence and death is significantly reduced when adjuvant chemotherapy and/or hormonal therapy is added to treatment. As new strategies are incorporated, one of the continued controversies in patient management is whether adjuvant anthracyclines should be the preferred treatment for all patients. Data from randomized and translational clinical trials have become available and are helping to elucidate the proper role of anthracyclines, as well as their acute and long-term toxicities. In most situations, an anthracycline is currently preferred, but other single and combination chemotherapies are currently under evaluation and appear promising for use in the adjuvant setting. Continued breast cancer research using molecular markers (such as topoisomerase II-alpha and gene clusters) as predictors of treatment response, could help individualize decisions regarding whether to incorporate anthracyclines into adjuvant therapy regimens.