Simple SummaryOur growing aging population and increased prevalence of obesity have become an emerging health problem as these conditions lead to the development of related diseases. Specifically, obesity and aging are associated with cardiovascular disease and a decline in cognitive function underlying the inflammatory mechanisms. However, the literature regarding how both interact and impact these complex physiological processes across the lifespan remains to be elucidated. As such, this review discusses how obesity in aging adults mediates inflammatory, cardiovascular, and neurobiological effects of exercise in this population.AbstractObesity with advancing age leads to increased health complications that are involved in various complex physiological processes. For example, inflammation is a critical cardiovascular disease risk factor that plays a role in the stages of atherosclerosis in both aging and obesity. Obesity can also induce profound changes to the neural circuitry that regulates food intake and energy homeostasis with advancing age. Here we discuss how obesity in older adults impacts inflammatory, cardiovascular, and neurobiological functions with an emphasis on how exercise mediates each topic. Although obesity is a reversible disorder through lifestyle changes, it is important to note that early interventions are crucial to prevent pathological changes seen in the aging obese population. Lifestyle modifications such as physical activity (including aerobic and resistance training) should be considered as a main intervention to minimize the synergistic effect of obesity on age-related conditions, such as cerebrovascular disease.