The association of erectile dysfunction (ED) and cardiovascular disease is well-documented in the literature and both conditions share risk factors. Therefore, it is difficult to distinguish the effect of underlying disease and adverse effects of the drugs and/or interactions between ED drugs and drugs implemented for cardiovascular disease. The known interactions of systemic administered drugs for ED with drugs for cardiovascular disease are mainly pharmacodynamic. Thus, nitrates enhance the production of cyclic GMP and combined with phosphodiesterase type-5 inhibitors this can lead to severe hypotension. The same is the case for the treatment with phentolamine in patients treated with beta-adrenoceptor antagonists. Due to increased partial thromboplastin time, the risk of bleeding is enhanced for intracavernous alprostadil injection in heparin-treated patients. Pharmacokinetic interactions of clinical importance have been described for ED drugs with other therapeutic groups such as sildenafil with the antifungal drug, ketoconazole, and apomorphine with the antiparkinson drug, entacapon. Although sildenafil and antihypertensive dihydropyridines like amlodipine are metabolized by the same cytochrome P450 enzyme, CYP3A4 in the liver, the combination of these drugs does not exhibit a synergistic blood pressure lowering action. Unfortunately documentation concerning drug interactions is often poor and occasional.