The significance of the age-related decline of androgens remains unclear in terms of cardiovascular risk, mood and cognition, and prostatic health. Although much research has been undertaken in this area and men's health has received still more attention in the latest years, there are no data based on randomized controlled clinical studies in aging men investigating the long-term effects of androgen replacement therapy on various aspects of the cardiovascular system, the immune system, body composition, and the brain. In men receiving long-term androgen replacement therapy, the safety aspects regarding the prostate are also an area of clinical importance. In this paper we present an up-dated review of the experimental and clinical evidence of androgen deficiency and androgen replacement therapy on carbohydrate metabolism, on coagulation and fibrinolysis, inflammatory effects, effects on lipoprotein metabolism, direct arterial effects, effects on body composition, effects on cognitive function and mood, and prostatic effects. The evidence clearly shows that data for the most part are conflicting, with only very few randomized studies available.