This chapter discusses history of sildenafil—from angina to erectile dysfunction. Men, traumatized by a fear of impotence have turned to a host of natural aphrodisiacs, rituals and prayers, hormonal treatments and mechanical devices and a growing number of scientific (and pseudoscientific) drug to address the problem. In 1996, Nicholas K Terrett, Andrew S Bell, David Brown and Peter Ellis, working at Pfizer’s research facility in Kent, England tested one such compound known as compound UK-92,480 to treat hypertension and angina pectoris. It was found that, although the drug had little effect on angina, it could induce marked penile erections. It causes smooth muscle relaxation and dilatation of the helicine arteries, leading to vasodilation and increased inflow of blood into the spongy tissue of the penis causing an erection. The success story of sildenafil, expanding uses beyond treatment for erectile dysfunction are discussed.