Abstract The introduction and widespread adoption of the sentinel lymph node (SLN) biopsy procedure in the mid-1990s, dramatically changed the landscape of axillary nodal staging and management, ultimately leading to the avoidance of axillary node dissection (ALND) and its resultant co-morbidities for thousands of women with node negative breast cancer. For those found to have positive sentinel nodes, the landscape has again changed and many women with limited volume nodal disease, defined as 1 or 2 positive SLN, are now also offered the opportunity to avoid axillary node dissection, largely in favor of observation alone for those undergoing breast conservation therapy (BCT) or in favor of axillary radiation for those undergoing mastectomy. These changes reflect clinical application of the results of several important prospective randomized trials including ACOSOG Z011, IBCSG 23-01, and EORTC 10981-22023 AMAROS, each of which demonstrated equivalence between axillary node dissection and the alternative strategy of interest (observation or axillary radiation). The increasing use of neoadjuvant therapy, in both high-risk clinically node negative (cN0) disease and in clinically node positive (cN1) disease, represents further opportunities to individualize axillary management; yet decision making must take into account several caveats including the performance characteristics of the SLN procedure after neoadjuvant therapy, the molecular subtype of the primary tumor and the planned breast procedure. For patients with triple negative or HER2+ disease, the use of neoadjuvant therapy is associated with high rates of nodal pCR and therefore a lower likelihood of requiring an axillary node dissection in the cN1 cohort that converts to cN0 and undergoes a successful SLN biopsy procedure; however, in cN0 patients meeting eligibility criteria for avoidance of ALND in the aforementioned trials of upfront surgery, the use of neoadjuvant therapy may not significantly impact rates of ALND. Similarly, for patients with cN0 hormone receptor positive disease, upfront surgery (BCT or mastectomy) likely offers more opportunity for individualized management; whereas for those with cN1 disease, neoadjuvant therapy may result in downstaging of the axilla, although patient selection is critical as many patients with low to intermediate grade, node positive, hormone receptor positive disease are now being offered the opportunity to avoid chemotherapy in the adjuvant setting in favor endocrine therapy alone, and data on management of the axilla after neoadjuvant endocrine therapy are limited. In aggregate, the evolving literature on management of axilla represents a victory for patients and provides increasing support for the “less is more” approach that has emerged throughout the last decade. In daily clinical practice, the challenge lies in clear communication of the myriad of options and the interplay between tumor biology, systemic therapy and surgical decision making. Citation Format: King TA. Individualizing Management of the Axillary Nodes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PL3.