Contemporary treatment algorithms for erectile dysfunction (ED) involve the use of medical therapies such as phosphodiesterase type 5 (PDE5) inhibitors and intracavernosal injection therapy of vasoactive agents, as well as vacuum erection devices and penile prosthesis implants in medically refractory cases. However, the current therapeutic options only address the symptoms of ED and not the underlying pathogenesis that results in ED. Newer and novel ED therapies aspire to reverse ED conditions by preventing cavernosal fibrosis, promoting endothelial revascularization and modulating various neuro-hormonal pathways. Regenerative therapeutic strategies such as low-intensity shock wave, gene and cellular-based therapies, and penile transplants are designed to improve penile hemodynamics and revitalize the cavernosal smooth muscle to mitigate and/or reverse underlying ED. This state-of-art article evaluates current and emerging therapeutic options for ED.