The ideal sequencing of CT and radiation therapy in early-stage breast cancer treated with breast-conserving surgery and RT is not known. There is evidence that delaying CT might have an adverse impact on systemic control, while delaying RT might adversely affect local control. Concurrent CT and full-dose RT might minimize the above tradeoffs, but is associated with increased toxicity. Concurrent CT and reduced-dose RT is a novel approach to address these issues, but requires additional formal evaluation before clinical use. In the absence of definitive information, clinicians should balance each patient's risk for systemic recurrence and local-regional recurrence. For example, a patient with a large number of positive nodes but clearly negative margins would be an appropriate candidate for adjuvant therapy starting with CT and continuing with RT at the completion of CT. Alternatively, a patient with node-negative disease with close or focally positive margins might be an appropriate candidate for initiating RT sooner. Current treatment regimens which deliver CT in a "short" time period [i.e., Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) delivered in four 3-week cycles] may represent a reasonable tradeoff with regard to promptly starting systemic therapy while initiating RT within 3 months of surgery. It is possible that optimizing the way RT and CT are combined is important in achieving the highest survival rate and in reducing long-term adverse effects. There is unfortunately very little solid information from randomized clinical trials addressing this question, and considerable controversy remains regarding the optimal approach to integrating these modalities. Additional randomized clinical trials addressing this important clinical question are needed.