Diarrhea in patients with AIDS is a worldwide problem that can have a devastating impact on quality of life for the patient. Chronic diarrhea, usually defined as at least 4 weeks' duration, is more common in patients with low CD4-positive T-lymphocyte counts, signaling advanced immunosuppression. Some organisms, such as Microsporidia, usually cause diarrhea only in the immunosuppressed; others, such as Cryptosporidium, Salmonella, Shigella, and Campylobacter, which are capable of causing diarrhea in the immunocompetent population, produce more severe or prolonged infections in people living with AIDS. Familiarity with the most common pathogens in the clinician's region will help with diagnosis and treatment. Because treatment options vary widely depending upon the infectious agent, thorough microbiologic evaluation is warranted. A stepped diagnostic approach of stool cultures and specialized microscopy and stains for protozoa, followed by sigmoidoscopy or colonoscopy and duodenoscopy with biopsies for histopathological examination is recommended in all patients with persistent, disabling diarrhea who have a CD4 count of less than 200/mm3, and should be considered for those with higher counts on an individual basis. Treatment, tailored to the specific pathogen, may need to be prolonged in the most severely immunocompromised patients to prevent relapse or recrudescence. For patients taking antiretroviral therapy (especially protease inhibitors) in whom no infectious agent can be found, diarrhea may be due to the medications. Nonspecific antidiarrheal agents should be tried until one that suits the patient is found. The most essential component of any therapeutic strategy for a patient with AIDS-associated diarrhea is restoration of the underlying immunologic defect using highly active antiretroviral therapy.