We have reviewed the current status of primary chemotherapy for resectable breast cancer. Available findings indicate that the most immediate benefit of this treatment approach consists in an important tumor shrinkage, enabling to significantly increase the rates of breast conserving approaches. In spite of the logical and scientific rationale, available data from prospective randomized studies do not provide evidence of a clear superiority of primary chemotherapy over adjuvant chemotherapy. Nevertheless, the observed kinetic acceleration of micrometastases following noncurative surgical excision in animal studies represents a strong biologic evidence supporting primary chemotherapy. From a clinical perspective, primary chemotherapy with conventional regimens can induce a low to moderate rate of pathological complete remissions that appear to be an important marker of favorable treatment outcome. For this reason, well designed, prospectively randomized, large trials with drug regimens more effective than those used so far are mandatory to demonstrate the real worthiness of this newer treatment approach and to define the optimal timing of surgery and other locoregional modalities in respect to the long-term treatment outcome. Should there be no benefit to the use of primary drug treatment, then the biologic consequences of primary tumor removal, as observed in experimental models, are not likely to be of clinical significance. Nonetheless, since primary chemotherapy can achieve long-term results similar to those obtained with postoperative drug treatment while increasing the frequency of breast-sparing approaches, women can be offered a choice to maintain their body integrity. Should improved pathological complete remission rates from more effective regimens of primary chemotherapy translate into improved survival compared with the classical postoperative modality, then, regardless of the tumor diameter at diagnosis, our overall strategy for the management of operable breast cancer will require a radical departure from the traditional dogma.