Obesity, type 2 diabetes mellitus and the metabolic syndrome are major risk factors for cardiovascular disease. Studies have demonstrated an association between low levels of testosterone and the above insulin-resistant states, with a prevalence of hypogonadism of up to 50% in men with type 2 diabetes mellitus. Low levels of testosterone are also associated with an increased risk of all-cause and cardiovascular mortality. Hypogonadism and obesity share a bidirectional relationship as a result of the complex interplay between adipocytokines, proinflammatory cytokines and hypothalamic hormones that control the pituitary-testicular axis. Interventional studies have shown beneficial effects of testosterone on components of the metabolic syndrome, type 2 diabetes mellitus and other cardiovascular risk factors, including insulin resistance and high levels of cholesterol. Biochemical evidence indicates that testosterone is involved in promoting glucose utilization by stimulating glucose uptake, glycolysis and mitochondrial oxidative phosphorylation. Testosterone is also involved in lipid homeostasis in major insulin-responsive target tissues, such as liver, adipose tissue and skeletal muscle.