Chronic illness and its treatments can have a negative impact on sexual functioning. The mechanism of interference may be neurologic, vascular, endocrinologic, musculoskeletal, or psychologic. Patients may mistakenly perceive a medical prohibition to the resumption of sexual activity, or they may need advice on changes in sexual activity to allow satisfactory sexual functioning. Family physicians must be proactive in diagnosing and managing the alterations in sexual functioning that can occur with chronic illness. Patient education and reassurance are essential. Before sexual activity is resumed, patients with cardiovascular disease should be stratified according to risk. Patients with musculoskeletal disease should be educated about positional changes that may improve comfort during sexual activity. Psychosocial concerns should be addressed in patients with human immunodeficiency virus infection or acquired immunodeficiency syndrome. In patients with cancer, it is important to discuss sexual problems that may arise because of negative body image and the effects of chemotherapy. Patients who have disabilities can benefit from the use of muscle relaxants, technical adaptations, and expansion of their sexual repertoire.