Abstract: Erectile Dysfunction (ED) is a common condition in older men between the ages of 40 to 70 years caused by physiological and psychological factors. Among many methods used in ED treatment is orthodox pharmaceutical like Viagra, but many medicinal plants are used traditionally for the treatment of ED and infertility, one of which is Mondia whitei. The aim of this review is to analyze pathways of penile erection and scientific findings that support the traditional use of M. whitei to propose its possible mode of action as a potential aphrodisiac. Studies have shown that it significantly and progressively enhanced human spermatozoa in vitro, reduce mutant latency of sexually inexperienced male rats toward receptive female rats and increased frequency of penile erection in vivo. Crude extract of M. whitie at 200 mg kg-1 increases NOS activity with corresponding increased NO, cGMP levels in vivo supporting results from pre-incubation of carvernosal tissue in vivo with crude extract and its chloroform fractions with marked increased NOS activity; NO and cGMP levels at 0.01 mg g-1 tissue which oppose an in vitro studies with hexane extract (400 μg mL-1) that caused blockade of voltage-operated calcium channels. Mondia whitei may synergistically activating NOS for cGMP generation with cross activation of PKA to generate cAMP; block the receptor-operated and voltage-operated calcium channels to prevent entry of calcium during depolarization that completely abolished contractile effect of calcium to enhance penile erection. More importantly cGKI can be an interesting target for M. whitei for the treatment of ED in the development of new drug.