Obesity remains a major public health problem, affecting almost half of adults in the United States. Increased risk of cardiovascular disease (CVD) and CVD mortality are major obesity-related complications, and management guidelines now recommend weight loss as a key strategy for the primary prevention of CVD in patients with overweight or obesity. The recently demonstrated efficacy of some pharmacologic therapies for chronic weight management may encourage health care professionals to recognize obesity as a treatable serious chronic disease and motivate patients to re-engage with weight loss when previous attempts have been ineffective or unsustainable. This review article summarizes the benefits and challenges associated with lifestyle changes, bariatric surgery, and historical pharmacologic interventions in the treatment of obesity, and focuses on the current evidence for the efficacy and safety of the newer glucagon-like peptide-1 receptor agonist medications in the management of obesity and potential reduction of CVD risk. We conclude that the available evidence demonstrates glucagon-like peptide-1 receptor agonists should be strongly considered in clinical practice for the treatment of obesity and reduction of CVD risk in people with type 2 diabetes. If ongoing research proves glucagon-like peptide-1 receptor agonists to be effective in reducing the risk of CVD onset in patients with obesity, irrespective of type 2 diabetes status, it will herald a new treatment paradigm in this setting, and now is the time for health care professionals to better recognize the benefits of these agents.