The present article begins with an introduction to the role of Institutional Review Boards (IRBs) in research activities in general and proceeds to issues IRBs face with relation to special populations, including children and terminally ill individuals, as well as developmentally disabled and cognitively impaired persons. A historical overview of research with these special populations is included, and the report concludes with a real-world example of how IRB-related issues with developmentally disabled and cognitively impaired individuals are discussed and resolved.