Systemic testosterone levels fall about 1% each year in men. The reasons of such association are only partially known. A large body of evidence has demonstrated that hypogonadotropic or mixed hypogonadism is closely associated with type 2 diabetes mellitus (T2DM). On the other hand the association between Metabolic Syndrome (MetS) and hypogonadism is emerging. Since MetS is often present in patients with T2DM, we recently evaluated the different contribution of these two conditions in the pathogenesis of male hypogonadism. In a consecutive series of 1134 patients we demonstrated that, diabetes per se, independently of MetS, was not associated with hypogonadism. Alexander et al. has previously reported similar results in predicting CV diseases. The pathogenetic mechanisms involved in this issue are not completely understood, however it could be speculated that some factors associated with visceral adiposity, and upstream of insulin resistance, could contribute both to hypogonadism and CV diseases. Whether or not low testosterone could play a pathogenetic role in CV disease is under debate. However, it should be recognized that meta-analysis reports have clearly demonstrated that testosterone replacement therapy determines a reduction of fat mass and an improvement of lipid profile. Although lifestyle approach and weight loss are characterized by an improvement of CV profile as well as by an increase of testosterone, recently it has been reported that the combination of testosterone therapy and lifestyle approach determine a better outcome in glycometabolic control, weight loss and lipid profile in patients with T2DM.