Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See complete disclaimer in Appendix 1 and Appendix 2 for more. Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline . PURPOSE To provide evidence-based recommendations for patients with stage IV non–small cell lung cancer with driver alterations. METHODS This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Eight new RCTs were identified in the latest search of the literature to date. RECOMMENDATIONS Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients based on targetable driver alterations. Additional information is available at www.asco.org/living-guidelines .