Early randomized trials of the addition of neoadjuvant chemotherapy (NACT) to the treatment regimen of patients with breast cancer failed to demonstrate an improvement in overall survival compared with conventional adjuvant therapy; nevertheless, the increased opportunities for breast conservation, owing to downstaging of the primary tumour, and enthusiasm regarding the potential to tailor systemic therapy based on responses observed in the neoadjuvant setting, resulted in the adoption of this approach as a useful clinical tool. That the effectiveness of NACT varies by molecular subtype is becoming increasingly clear, and although the potential of tailoring adjuvant systemic therapy based on treatment response before surgery remains to be realized, the increasing rates of pathological complete response following NACT have had a considerable impact on locoregional treatment considerations. For example, NACT reduces the need for mastectomy and axillary lymph-node dissection, thus decreasing the morbidity of surgery, without compromising outcomes. However, selection of the ideal candidates for preoperative chemotherapy remains critical, and personalizing local therapy based on the degree of response is the subject of ongoing clinical trials. This article reviews the current issues surrounding surgery of the breast and axilla in patients with breast cancer receiving NACT.