The rules and regulations pertaining to human subjects in research have evolved in response to ethical concerns for the protection of the rights and welfare of such subjects. However, investigators quite often are not well informed on what is required of them in the conduct of their clinical studies. Failure to be provided with sufficient information may be part of the problem, but the nature of such rules and regulations and their diversity and complexity certainly are sources of confusion. This article presents an overview of some of the major components and processes involved in the implementation of the federal regulations. It is hoped that this presentation will lead to a better understanding of the roles of the investigator, the institutional review boards, and the institutional and the federal agencies involved in the protection of human research subjects.