Although using phosphodiesterase type 5 inhibitors to treat erectile dysfunction has been highly effective in clinical trials, many men do not achieve their desired goals and stop using the medication after a few attempts. The notion of optimizing response to pharmacologic interventions is relatively new to clinicians. Restoration of healthy erectile function is a complex action that requires proactive management from physicians. The following must be considered to optimize response to treatment: 1) the accuracy of the diagnosis, 2) encouraging realistic expectations, 3) choosing the appropriate type of phosphodiesterase type 5 inhibitor, 4) using the medication effectively and titrating the dose when needed, 5) following-up with appropriate re-education and encouragement, and 6) offering adjunctive pharmacologic or psychological support, ideally involving the partner.