The description of the nerve-sparing technique of radical prostatectomy by Walsh was one of the major breakthroughs in the surgical treatment of prostate cancer in the 20(th) century. However, despite this advance and consequent technological refinements to nerve-sparing surgery, a large proportion of men still suffer from erectile dysfunction (ED) as a complication of prostatectomy. A plethora of therapeutic approaches have been proposed to optimize erectile function recovery in these patients. Several preclinical and translational studies have shown benefits of therapies including PDE5 inhibitor (PDE5I) treatment, immunomodulation, neurotrophic factor administration, and regenerative techniques, such as stem cell therapy, in animal models. However, most of these approaches have either failed to translate to clinical use or have yet to be studied in human subjects. Penile rehabilitation with PDE5Is is currently the most commonly used clinical strategy, in spite of the absence of solid clinical evidence to support its use.