The management of breast cancer has undergone remarkable change over the past two decades. A therapeutic revolution has been fueled by the results obtained from prospective randomized clinical trials. The National Surgical Adjuvant Breast and Bowel Project (NASBP) protocols B-04 and B-06 have clearly demonstrated the efficacy of breast conserving surgery in Stage I and II breast cancer. Through fourteen (NSABP B-04) and 9 years (NSABP B-06) of follow-up respectively, three is no significant difference in either distant-disease free or overall survival between the breast-preserving option and breast removal procedures. These studies not only establish breast-sparing surgery as the preferred local-regional procedure, but more importantly validate the biologic hypothesis governing its use, i.e. breast cancer is a systemic disease and nuances in loco-regional therapy have little impact on survival. Building on this concept, the NSABP instituted clinical trials in the early 1980's designed to evaluate the worth of systemic therapy in node-negative breast cancer. NSABP protocol B-13 examined sequentially administered methotrexate and 5-fluorouracil (MF) versus observation alone in estrogen receptor (ER) negative patients while NSABP protocol B-14 evaluated the worth of tamoxifen versus placebo in ER positive patients. Both of these studies demonstrate a benefit for adjuvant therapy. One can only conclude that adjuvant therapy has altered the natural history of node negative breast cancer. Further clinical trials should expand on advances already achieved and attempt to target therapy to those patients most likely to develop a treatment failure.