Purpose of review Although oral type 5 phosphodiesterase inhibitors are considered as first-line therapy for the majority of causes of erectile dysfunction, because of their high efficacy, ease of use, and acceptable safety-profile, there are some who fail to respond, mainly because of end-organ failure. This communication reviews the management of sildenafil failures in light of recent advances. Recent findings Sildenafil failures can be attributed to either lack of efficacy or side effects; issues may involve the physician, patient, and his partner. Physicians may contribute to sildenafil failure and discontinuation because of inadequate instructions, lack of adequate follow-up, suboptimal dosing, lack of adequate trial, and insufficient clarification about safety issues. Studies have demonstrated that progression of endothelial dysfunction and diminished cavernosal smooth-muscle content are recognized organic factors which cause end-organ dysfunction and ultimately treatment failure. Summary Proper counseling, medication optimization, and modifying associated risk factors can provide success in men who had initially failed sildenafil therapy for erectile dysfunction. Other treatment modalities that may be considered when sildenafil failure occurs include vacuum devices, intraurethral, and intracavernosal administration of vasoactive drugs alone or combined with sildenafil. Penile prosthesis implantation is considered as a last resort, if all first-line and second-line therapies fail.