Penile erection is a complex neurohumoral-hemodynamic phenomenon. Stimulation of sacral parasympathetic or cavernous nerves causes erection. Various neurotransmitters and neuropeptides are known to be key mediators of erection. Non-adrenergic, non-cholinergic neurotransmission is also a critical player in penile erection. Male erectile dysfunction (MED) is multifactorial in origin wherein stress, hypertension, hypercholesterolemia, diabetes mellitus, cigarette smoking, and aging are implicated. Different treatment options available are psychosexual counseling, use of external vacuum devices, vascular surgery, penile prosthesis, intracavernous injection therapy, and medication. Bioassay explains isolated tension studies in organ bath. Penile erection is a consequence of three simultaneous hemodynamic events, such as increase arterial flow, sinusoidal relaxation, and venous outflow restriction. Vasculogenic impotence is an important clinical issue, which demands thorough investigation. Model for arteriogenic impotence is discussed. Penile vascular smooth muscle relaxation increases inflow of arterial blood and distension of sinusoids leading to erection. Model for atherosclerotic impotence is explained. Studies have associated obstruction of the arterial supply to the corporal bodies because of atherosclerotic vascular disease to impotence in humans. Pelvic or perineal trauma from bicycle accidents is known to cause focal lesion of the common penile or cavernous artery leading to post-traumatic arteriogenic erectile dysfunction. Model for venous incompetence induced impotence is discussed. The cavernous nerve is identified by electrostimulation and bipolar cuff electrodes are placed around it for inducing erection. In a healthy animal with robust arterial flow, minor venous leakage does not have prominent impact on erectile response. This model sheds light on the assessment criteria set for the diagnosis of vasculogenic impotence in humans.