Erectile dysfunction (ED) is a widespread, age-related medical condition that affects > 50% of men aged 40 - 70 years. Pharmacotherapy with orally available phosphodiesterase 5 (PDE5) inhibitors offers a convenient and simple approach to treatment. Results of numerous clinical trials have demonstrated significant efficacy in restoring the ability to achieve and sustain an erection, and adverse side effects are generally mild-to-moderate in severity. Vardenafil is a highly selective, potent PDE5 inhibitor developed for the treatment of ED. The potency and selectivity of vardenafil for PDE5 and other PDE isoforms have been evaluated in vitro and in vivo and compared with other compounds in the class. This review will discuss the findings of biochemical, in vitro and in vivo experiments that indicate the superior potency and high selectivity of vardenafil.