Stage III breast cancer encompasses a heterogeneous group of patients. According to the American Joint Committee on Cancer (AJCC) these tumors include stage IIIA and stage IIIB disease, the first generally being operable but the second inoperable. Patients with inflammatory breast cancer are also included in stage IIIB disease, and these patients have the worst prognosis. Multidisciplinary therapy has become the treatment of choice for these patients. Primary or neoadjuvant chemotherapy, followed by locoregional therapy, either surgery, radiotherapy or both, is now an accepted strategy. Most patients achieve a response to chemotherapy, resulting in downstaging of the tumor, and 5-year-survival rates have improved from 10-20% with local therapy alone to 30-60% with the multidisciplinary approach. Although many prospective, mainly phase II trials have been performed in stage III breast cancer, the optimal treatment scheme still has to be established. The role of new therapeutic strategies such as high-dose chemotherapy with hematopoietic stem cell rescue and higher dose intensity regimens with hematopoietic growth factors is currently under investigation. This article will review the literature and discuss our own research in this area.