Erectile dysfunction (ED) has many definitions, one of these accepted definition that the male is unable to initiate and/or preserve an erection for ideal sexual intercourse satisfying for both partners. There are many lines for ED treatment, oral phosphodiesterase type 5 inhibitors (PDE5Is) represent the corner stone for ED treatment. Intra cavernous injections, vacuum constriction device & surgical implantation of penile prosthesis are another methods for ED treatment. Authors failed to define exactly the failure of PDE5-I therapy in ED. However, many reviews reported two types of PDE5Is non responders. As regard the cause making ED patients non responders to PDE5Is, multiple etiological factors have a role. Four strategies were reported about in literatures as trial to solve PDE5i non responders problem including lifestyle adjustments, psychological assessment, comorbidities treatment & non drug therapeutic interventions.Patient counseling to know and resolve patients' concerns and ensure the hopped success of treatment. Good communication and regular follow up should be established.