Chronic diarrhea is one of the hallmarks of advanced human immunodeficiency virus (HIV) disease. The symptoms of this complication are troublesome, have a significant impact on the patient's quality of life, and in severe cases can lead to extreme abnormalities in fluids and electrolytes and can even cause death. The workup for AIDS-associated diarrhea is often frustrating and frequently unrewarding. However, during the last 10 years, much has been learned about the causes of diarrhea; while treatment is still often ineffective, some advances have been made. Dr. John G. Bartlett and his colleagues in the Department of Medicine at Johns Hopkins University School of Medicine have been responsible for many of these advances. In this AIDS Commentary, these experts discuss recent advances that have enhanced our understanding of chronic diarrhea in HIV-infected persons and offer their recommendations for the most efficient and effective approach to managing these patients.