Melanocortinergic agents are currently being investigated for a possible therapeutic role in male and female sexual dysfunction. These investigations were sparked by findings that systemic administration of a synthetic analog of alpha-MSH, MT-II, causes penile erections in a variety of species, including humans. Several other melanocortinergic agents including HP-228, THIQ, and bremelanotide (PT-141) have since been shown to have erectogenic properties thought to be due to binding to melanocortin receptors in the central nervous system, particularly the hypothalamus. Bremelanotide, a nasally administered synthetic peptide, is the only melanocortinergic agent that has been clinically studied in both males and females. Data from Phase II clinical trials of bremelanotide support the use of melanocortin-based therapy for erectile dysfunction. Studies using animal models have demonstrated that pre-copulatory behaviors in female rats analogous to sexual arousal are evoked, and preliminary clinical data also suggest a role in promoting sexual desire and arousal in women. Based on bremelanotide clinical experience, administration of a melanocortin agonist is well tolerated and not associated the hypotension observed with phosphodiesterase-5 inhibitors currently used to treat erectile dysfunction. This review discusses investigations of melanocortin agonists for the treatment of sexual dysfunction with emphasis on proposed sites and mechanisms of action in the central nervous system that appear to be involved in melanocortinergic modulation of sexual function. Current research validates use of melanocortinergic agents for the treatment of both male and female sexual dysfunction.