Epidemiological studies correlated the age-related decline of serum testosterone levels to the concomitant increase of cardiovascular diseases, osteoporosis and bone fractures. For this reason, testosterone replacement therapy (TRT) in older men with late-onset hypogonadism has been advocated. Testosterone has an anti-resorptive effect that may increase bone density at lumbar spine. Androgens may also have cardio-protective effects by improving endothelial function and reducing the risk factors for atherosclerosis. It has been proposed that atherosclerosis and osteoporosis share common pathophysiological mechanisms. The role of inflammatory cells, citokynes and calcium deposition into the vascular walls has been reviewed to explore the causal nexus between these frequently associated diseases. Experimental studies indicate that a deregulation in the commitment of pluripotent mesenchimal stem cells toward specialized phenotypes might participate in the development of these conditions. The crossed-over beneficial effect of bisphosphonate on the cardiovascular system and statins on bone metabolism supports the research for a unitary pharmacological approach to both conditions. The findings that androgens regulate mesenchimal cell differentiation, as well as body composition, lipid profile and bone metabolism, have claimed a role for TRT in aging men with late onset-hypogonadism.