We have now completed the second decade of the acquired immunodeficiency syndrome (AIDS) that first came to attention in 1981 . The early years of the epidemic were devoted to describing the vast spectrum of, and defining optimum treatments for, the complications of AIDS. Over the past 10 years, there has been intense investigation into the virology of the human immunodeficiency virus (HIV) and, consequently, rapid progress in our understanding of the pathogenesis of this devastating worldwide infectious disease. These efforts have culminated in the development of highly active antiretroviral therapies, termed HAART, which have profoundly changed the paradigms for management of HI V-related complications including those involving the gastrointestinal tract [2, 3]. Because of the widespread availability of these drugs and access to care  the fall in AIDS-related morbidity and mortality has been most pronounced in the developed world, whereas in contrast, and for the foreseeable future, complications related to HIV-associated immunodeficiency will continue unabated in developing countries [1, 5]. Before the development of HAART, gastrointestinal disorders occurred almost uniformly in patients with AIDS. Problems referable to the colon, usually diarrhea, were observed in 50% or more of patients at some point during the course of HIV and AIDS . Although opportunistic infections and neoplasms comprise the majority of the colonic disorders in these patients, a number of cases of inflammatory bowel disease (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), have been described [6-22]. In addition, an idiopathic inflammatory disease of the colon, apparently distinct from IBD, has also been recognized [23, 24]. Given the potential for confusion clinically, endoscopically, and pathologically between opportunistic infections of the colon and IBD, an appreciation of the clinical presentation, differential diagnosis, and management of IBD in HIV-infected patients is important. In this chapter the relationship of HIV infection and IBD will be explored, focusing on the pathogenesis of IBD and what lessons we can learn from coexistent HIV infection; the chapter will review the clinical presentation and relationship to immunodeficiency of the reported patients with HIV infection; outline the differential diagnosis of IBD in the setting of HIV; and review management. Finally, criteria will be proposed for the diagnosis of idiopathic IBD in the setting of HIV infection. © 2005 Springer Science+Business Media, Inc.