Neoadjuvant treatment of breast cancer has become established as the safe and often effective therapeutic approach of choice for larger primary and for locally advanced breast cancer. The neoadjuvant approach offers the advantages of downstaging the disease, potentially reducing the extent of surgery and in an era of individualization of therapy, testing the efficacy of therapy administered to patients. The preoperative setting is also an effective way to study the activity of novel agents or therapeutic combinations in vivo against human breast cancer. For new therapies, preoperative trials avoid the issue of adaptive resistance and pretreatments that can be problematic in the advanced disease setting. For evidence of a drug targeting the cancer in vivo, comparisons of endocrine therapy, chemotherapy agents and/or targeted agents can provide data on activity and efficacy with a much shorter time frame and many fewer patients than for adjuvant trials; effects seen in neoadjuvant trials may even reflect what is found in the adjuvant setting. Patient benefits from the neoadjuvant approach may be greatest for those who experience complete pathologically documented response (and the consequent survival benefits) and women for whom breast conservation, rather than mastectomy, becomes possible.