Evidence from clinical studies suggests that patients with low testosterone levels are at increased cardiovascular disease risk. Even though the exact mechanisms remain poorly understood, a low plasma testosterone level is associated with a pro-atherogenic lipid profile, insulin resistance and increased levels of pro-inflammatory mediators and vascular dysfunction, which is typically observed in patients with hypogonadism. Furthermore, recent evidence suggests that testosterone deficiency has also direct adverse effects on the endothelium and nitric oxide (NO) bioavailability. Observations from studies in patients with hypogonadal hypogonadism imply that the mechanisms of endothelial dysfunction related to testosterone deficiency may involve changes in asymmetric dimethylarginine (ADMA) levels, a known endogenous inhibitor of NO synthase. Evidence suggests that testosterone replacement therapy is not only a safe but also an effective means to reduce atherosclerotic risk and reverse endothelial dysfunction in patients with hypogonadal hypogonadism. Further research in the field is expected to clarify whether changes in ADMA metabolism constitute the central mechanism through which a low testosterone level leads to endothelial dysfunction.