Postmenopausal women represent an important target population in need of preventative cardiometabolic approaches. The loss of estrogen following the menopause eliminates protections against metabolic dysfunction, largely due to its role in the health and function of adipose tissue. In addition, some studies associate the menopause with reduced physical activity, which could potentially exacerbate the deleterious cardiometabolic risk profile accompanying the menopause. Meanwhile, exercise has adipocyte-specific effects that may alleviate the adverse impact of estrogen loss through the menopausal transition period and beyond. Exercise thus remains the best therapeutic agent available to mitigate menopause-associated metabolic dysfunction and represents a vital behavioral strategy to prevent and alleviate health decline in this population.