The most important determinant of prognosis for patients with breast cancer is the status of the axillary lymph nodes. Axillary lymph node dissection (ALND) has been performed for over a century to stage the cancer, achieve regional control, and perhaps improve survival. In accordance with tradition, ALND has been performed on all patients with the diagnosis of invasive breast cancer. In the early 1990s, this dogma was challenged because of the significant morbidity associated with ALND (paresthesia, extremity lymphedema) and the fact that greater than 50% of all breast cancers are node negative. A less morbid but highly accurate staging procedure, lymphatic mapping and sentinel lymph node biopsy (SNB) was introduced. Currently, the de facto standard of care in breast cancer is to perform LM and SNB in patients with small tumors and clinically negative axilla. While numerous methodological issues are being raised, the utility of LM and SNB identification continues to expand. In the current review we assess the application of this technique to locally advanced breast cancer (LABC) and neoadjuvant chemotherapy. What role does SNB play in locally advanced disease? Is LM and SNB accurate for patients with advanced disease? What influence do axillary metastases have on further treatment? What is the role of SNB in the planning for neoadjuvant patients? The skillful management of patients with breast cancer lies in the delicate balance between maximizing the efficacy of treatment and minimizing its morbidity and failure.