Sexual dysfunction is a frequent complication of treated and untreated cardiovascular disease. In fact, ∼30% of hypertensives have been found to suffer from erectile dysfunction (ED) resulting from arterial dysfunction. Recent evidence has suggested that ED may be an early indicator of subclinical cardiovascular disease. In women, the evidence is similar, but more limited, showing that in hypertensive patients there is an increased prevalence of sexual dysfunction involving decreased vaginal lubrication, decreased orgasm, and increased pain. Clouding the issue, however, is that some antihypertensive agents may induce sexual dysfunction in hypertensives with normal sexual function. In contrast to the chronic treatments used in hypertension, therapies for ED involve acute treatments (none currently approved for women) targeting vasodilation of penile arteries, resulting in erection. Common to the treatment of hypertension and ED is that the current therapies were not designed to target underlying disorders of local, neural, vascular, or endocrine origin. In fact, while blood pressure is lowered, and erectile responses are improved with the respective therapies, the causal abnormalities may progress thereby limiting the long-term effectiveness of the medication. Some antihypertensive agents have been shown to have additional effects beyond blood pressure reduction and their impact on sexual function is a key focus of this review. This review examines the current and future strategies for treatments of male and female sexual dysfunction and the potential for therapeutic modalities that go beyond the recovery of the responses by targeting the fundamental mechanisms common to both sexual dysfunction and cardiovascular disease.