Optimal regional management in breast cancer patients has yet to be established. In patients who are clinically node-negative, but sentinel lymph node biopsy (SLNB)-positive, the treatment paradigm has shifted toward the de-escalation of further axillary management. In patients with 2 or fewer positive sentinel nodes, the standard of practice has shifted away from complete axillary lymph node dissection (ALND) as a result of the ACOSOG Z0011 trial. The role of regional nodal irradiation (RNI) to the axilla, supraclavicular and internal mammary regions has also been investigated in the setting of positive SLNB in trials such as the MA20 and EORTC 22922. Having shown evidence of benefit in locoregional control, efforts are now focused on comparing ALND with RNI in patients with limited nodal disease. Results of early trials such as AMAROS suggest noninferiority of radiotherapy. In patients with node-positive or locally advanced disease, neoadjuvant chemotherapy (NAC) is often used to downsize or downstage the disease. The utility of SLNB after NAC has been investigated, with discordant results reported from a number of trials. Current trials in progress seek to validate the noninferiority of RNI compared with ALND in patients with limited nodal disease, or in some trials, the complete omission of further axillary management. There is a global paradigm shift toward de-escalation of axillary management on the basis of recent evidence suggesting lack of benefit from overaggressive treatment. In this review we aim to summarize the seminal trials addressing regional management in breast cancer to illustrate this fact.