Drugs acting within the central nervous system (CNS) that reduce the sympathetic antierectile flow and enhance the parasympathetic proerectile flow to the penis may restore penile erection in cases of erectile dysfunction of both psychogenic and organic origin. The best characterized of such drugs is the dopaminergic agonist apomorphine, which acts on the hypothalamus and, perhaps, the autonomic nuclei in the spinal cord. Other drugs that target the CNS and have been registered and tested are the a(2)-adrenoceptor antagonists yohimbine and delequamine, the alpha-melanocyte-stimulating hormone agonist melanotan II, and the serotonin reuptake inhibitor trazodone. Androgens also may influence sexual behavior by acting within the CNS, notably by modifying the neurotransmitter system targeted by these drugs. Our knowledge of the mode of action of CNS drugs comes mainly from experiments on rodents. Consequently, explanations regarding the way they work in humans are only speculative.