Purpose: The American Society of Breast Surgeons (ASBrS) sought to provide an evidence-based guideline on the use of neoadjuvant systemic therapy (NST) in the management of clinical stage II and III invasive breast cancer. Methods: A comprehensive nonsystematic review was performed of selected peer-reviewed literature published since 2000. The Education Committee of the ASBrS convened to develop guideline recommendations. Results: A performance and practice guideline was prepared to outline the baseline assessment and perioperative management of patients with clinical stage II–III breast cancer under consideration for NST. Recommendations: Preoperative or NST is emerging as an important initial strategy for the management of invasive breast cancer. From the surgeon’s perspective, the primary goal of NST is to increase the resectability of locally advanced breast cancer, increase the feasibility of breast-conserving surgery and sentinel node biopsy, and decrease surgical morbidity. To ensure optimal patient selection and efficient patient care, the guideline recommends: (1) baseline breast and axillary imaging; (2) minimally invasive biopsies of breast and axillary lesions; (3) determination of tumor biomarkers; (4) systemic staging; (5) care coordination, including referrals to medical oncology, radiation oncology, plastic surgery, social work, and genetic counseling, if indicated; (6) initiation of NST; (7) post-NST breast and axillary imaging; and (8) decision for surgery based on extent of disease at presentation, patient choice, clinical response to NST, and genetic testing results, if performed.