Of the current options available to treat erectile dysfunction, oral phosphodiesterase type 5 (PDE5) inhibitors are the recommended first-line treatment. This review compares the three currently licensed PDE5 inhibitors: sildenafil citrate (sildenafil), vardenafil HCl (vardenafil) and tadalafil. All three drugs have similar efficacy and toxicity profiles. Sildenafil and vardenafil have similar molecular structures, but tadalafil is structurally different, which is reflected in its pharmacokinetic profile. With regard to the onset of action, achievement of an erection that leads to successful intercourse has been reported for 35% of patients treated with sildenafil within 14 min, 21% of patients treated with vardenafil within 10 min and 16% of patients treated with tadalafil within 16 min. Sildenafil and vardenafil both have half-lives of approximately 4 h but the half-life of tadalafil is 17.5 h. Another difference between the PDE5 inhibitors is that food, especially fatty food, affects the pharmacokinetic profiles of sildenafil and vardenafil, but not that of tadalafil. These pharmacokinetic differences among the PDE5 inhibitors may underlie patient preference, an important and emerging aspect of ED therapy.