Treatment of locally advanced noninflammatory breast cancer has changed markedly over the past 50 years. Haagensen's description of the clinical signs that define inoperable and operable tumors was the first realization that radical surgery alone could not cure the majority of women with locally advanced disease. Studies of the use of local therapy alone (surgery or radiation therapy) confirmed that most patients developed both distant metastatic disease and a high rate of local-regional failure. Combination surgery and radiation therapy regimens improved local control but did not influence long-term survival. The advent of successful multimodal regimens incorporating systemic treatment (chemotherapy or chemohormonal therapy) as well as local therapy (surgery and radiation) has significantly improved disease-free and overall survival as well as local-regional control. The benefits of neoadjuvant and adjuvant chemotherapy regimens have been debated. Neoadjuvant therapy allows clinical and pathologic assessment of tumor response to the chemotherapy regimen. In addition, local-regional control seems to be improved, and reductions in the size of the primary tumor allow breast-preserving procedures, even in patients initially not believed to be candidates for resection. Longer follow-up of these conservatively treated patients will be needed, however, to determine whether local-regional control is preserved.