Chronic HIV-associated diarrhea is currently a field in flux. Improved noninvasive diagnostic tests, improved pathogen-specific regimens, and better empiric therapies may change some of the assumptions used to select algorithms for diagnostic evaluation and management. Any shift in the cause of diarrhea from pathogen-associated to idiopathic or a reduction in the overall incidence of diarrhea would have considerable impact. It is unclear how significant the problem of pathogen relapse in previous responders will become. Existing studies reviewed in this article show that the high diagnostic yield of endoscopy when stool tests are negative, coupled with significantly better outcomes when pathogens are identified, support the current practice of routine endoscopic evaluation. There currently are scant data on the economic impact of HIV-associated diarrhea as it relates to pathogen-specific and empiric therapy in the era of protease inhibitors. Such data would be integral to future evaluation of the impact of diagnostic and therapeutic strategies.