Common in the medically ill, sexual dysfunction results from disruption of one or more stages of the sexual response cycle. Increased understanding of sexual pathophysiology and the psychosocial forces whereby diseases impede normal function promotes more informed treatment choices. This review focuses on the pathophysiology, impact, and treatment options of sexual dysfunction in men and women with spinal cord injuries, multiple sclerosis, dementia, hypertension, heart disease, stroke, cancer, and HIV/AIDS.