Both observational and interventional studies suggest an important role for physical activity and higher fitness in mitigating the metabolic syndrome. Each component of the metabolic syndrome is, to a certain extent, favorably influenced by interventions that include physical activity. Given that the prevalence of the metabolic syndrome and its individual components (particularly obesity and insulin resistance) has increased significantly in recent decades, guidelines from various professional organizations have called for greater efforts to reduce the incidence of this condition and its components. While physical activity interventions that lead to improved fitness cannot be expected to normalize insulin resistance, lipid disorders, or obesity, the combined effect of increasing activity on these risk markers, an improvement in fitness, or both, has been shown to have a major impact on health outcomes related to the metabolic syndrome. Exercise therapy is a cost-effective intervention to both prevent and mitigate the impact of the metabolic syndrome, but it remains underutilized. In the current article, an overview of the effects of physical activity and higher fitness on the metabolic syndrome is provided, along with a discussion of the mechanisms underlying the benefits of being more fit or more physically active in the prevention and treatment of the metabolic syndrome.