This review focuses on the prevalence, causes, evaluation, and treatment of headache in individuals infected with human immunodeficiency virus type 1 (HIV-1). Headaches, one of the commonest medical complaints in the general population, occur frequently in patients infected with the HIV-1. HIV-related headaches can occur at any time during the infection: at seroconversion, during the incubation period, in patients with symptomatic HIV-1 infection, or after an AIDS-defining illness. Causes of HIV-related headaches include HIV-1 itself, opportunistic conditions, or HIV-specific medications. Migraines, tension-type headaches, depression, and substance abuse enter into the differential diagnosis, particularly in the early stages of disease. The headaches seen in this population reflect a complex web of interactions imposed by immune competency, multiple etiologies, treatments, and premorbid conditions. Prompt recognition and early treatment of headache is essential since it may improve quality of life and, depending on the diagnosis, prolong survival. Physicians need to be alert and adaptable when assessing HIV-infected individuals with headache since multiple causes can exist in the same patient and new syndromes, complications, and investigational drugs are continually being identified.