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The past few decades have seen an increase in both the role and the complexity of neoadjuvant therapy for breast cancer. Neoadjuvant therapy was initially described as systemic chemotherapy for inflammatory or locally advanced breast cancer but now entails a combination of chemotherapy, endocrine therapy, and targeted therapy. Neoadjuvant systemic therapy is employed for inoperable inflammatory and locally advanced breast cancer, and also for patients with operable breast cancers who desire breast-conserving therapy (BCT) but are not candidates based on the initial size of the tumor in relation to the size of the breast. Neoadjuvant therapy in this subset of patients may impact the surgical options. This review will summarize the benefits of neoadjuvant systemic therapy and implications for BCT, the timing of sentinel node biopsy, and the utility of magnetic resonance imaging (MRI) to predict response to therapy.