Purpose of Review <p>This review summarizes the pharmacologic profiles, clinical trial evidence, and practical considerations for the use of first-generation obesity medications phentermine, orlistat, phentermine/topiramate extended-release, bupropion/naltrexone sustained-release, and liraglutide 3.0&#xa0;mg. Understanding the mechanisms, benefits, and limitations of these agents is essential for delivering comprehensive cardiometabolic care.</p> Recent Findings <p>First-generation obesity medications continue to play an important role in clinical practice. These agents can be highly effective in appropriately selected patients. While mean weight loss is less than newer incretin-based therapies, trial data demonstrate that a substantial proportion of individuals on first-generation agents achieve ≥ 10% total body weight loss.</p> Summary <p>First-generation obesity medications represent a cost-effective, evidence-based component of comprehensive obesity care—and remain critical tools to address atherosclerosis and other cardiometabolic complications of obesity.</p>