Erectile dysfunction (ED) affects over 50% of men between 50 and 70 years of age, and 40% of men aged about 40 years suffer from some form of erectile dysfunction. ED, with more than 100 million sufferers in the world, has become a serious disease besetting the male patients. Great strides have been achieved in understanding the pathogenesis and potential therapeutics of ED over the past two decades. The development of phosphodiesterase type 5 (PDE5) inhibitors has revolutionized the treatment of ED, but they are not as effective on ED related with diabetes, post-prostatectomy condition and severe veno-occlusive disease. As a potential therapeutic option for ED, gene therapy might provide an effective means. This article presents an overview on the progress of gene therapy in the management of ED associated with diabetes, aging, nerve injury and vascular lesion.