Through diverse mechanisms, obesity contributes to worsened cardiometabolic health and increases rates of cardiovascular events. Effective treatment of obesity is necessary to reduce the associated burdens of diabetes mellitus, cardiovascular disease, and death. Despite increasing cardiovascular outcome data on obesity interventions, only a small fraction of the population with obesity are optimally treated. This is a primary impetus for this article in which we describe the typical weight loss, as well as the associated impact on both traditional and novel cardiovascular disease risk factors, provided by the 4 primary modalities for obtaining weight loss in obesity—dietary modification, increasing physical activity, pharmacotherapy, and surgery. We also attempt to highlight instances where changes in metabolic risk are relatively specific to particular interventions and appear at least somewhat independent of weight loss. Finally, we suggest important areas for further research to reduce and prevent adverse cardiovascular consequences due to obesity.