The treatment of erectile dysfunction (ED) has been revolutionised by new agents to inhibit the enzyme PDE5. The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of PDE5 that breaks down cGMP, the key pathway for the production of erectile function in humans. Many clinical studies, both pre- and post-marketing, have demonstrated the clinical efficacy and safety of sildenafil (Viagra, Pfizer) - the first approved selective PDE inhibitor for the treatment of ED. Sildenafil is inhibitory of PDE5 at a rate tenfold higher than for the next PDE (PDE6), which produces visual changes through the retinal rods. Its clinical effectiveness has been well documented in the majority of men with ED irrespective of aetiology. The aetiology of ED, also, does not appear to effect the function of sildenafil in relaxing corpus cavernosum smooth muscle tissue. Adverse events are usually associated with the vascular changes from PDE5 inhibition. These include headache and flushing. Each of these adverse events, however, declines with medication use. With the use of sildenafil, it has been clearly, clinically demonstrated that the selective inhibition of PDE5 is an appropriate, effective, safe method for the treatment of ED of all aetiologies and severities.