Neoadjuvant chemotherapy provides clinical outcomes equivalent to those achieved when the same regimen is provided in the adjuvant setting. The therapeutic response to neoadjuvant treatment may include a reduction in tumor burden that alleviates the morbidity associated with locoregional therapy. Important prognostic information can be gained based on the response to treatment and knowing the quantity and biology of the residual disease. The evaluation of investigational agents in the neoadjuvant setting is of particular value for accelerating drug development. This review highlights landmark trials and contemporary perspectives on neoadjuvant chemotherapy and hormonal therapy, treatment response as a prognostic biomarker, use of the neoadjuvant paradigm for new drug development, and clinical advances in neoadjuvant therapy by molecular subtype of breast cancer.