Reproduction is a fundamental process for the species maintenance and the propagation of genetic information. The energy expenditure for mating is overtaken by motivational stimuli, such as orgasm, finely regulated by steroid hormones, gonadotropins, neurotransmitters and molecules acting in the brain and peripheral organs. These functions are often investigated using animal models and translated to humans, where the androgens action is mediated by nuclear and membrane receptors converging in the regulation of both long-term genomic and rapid non-genomic signals. In both sexes, testosterone is a central player of this game and is involved in the regulation of sexual desire and arousal, and, finally, in reproduction through cognitive and peripheral physiological mechanisms which may decline with aging and circadian disruption. Finally, genetic variations impact on reproductive behaviours, resulting in sex-specific effect and different reproductive strategies. In this review, androgen actions on sexual desire are evaluated, focusing on the molecular levels of interaction.