Investigators from diverse racial and ethnic backgrounds are grossly underrepresented in the nation's biomedical research enterprise. Projections of current demographic trends suggest that population growth rates of minority populations will outpace that of the Caucasian population by 2060. Thus, this workforce will remain a poor reflection of the U.S. population. As a result of this underrepresentation of all sectors of the U.S. populace, the majority of the HIV research involving minority populations-those disproportionately impacted by HIV infection-will be conducted by investigators who do not resemble them. Although this does not necessarily preclude scientifically valid and important research, it produces research without the important cultural and contextual issues that can enhance the utility and generalizability of specific findings or interventions. The goal of this review is to not only raise awareness of the small numbers of minority investigators engaged in biomedical research, but also to identify the challenges to recruiting and retaining these investigators. In this article, while we discuss issues of diversity in general, the focus will be upon the mental health aspects of the HIV epidemic for illustrative purposes: to demonstrate the issues associated with enhancing investigator diversity as a strategy for remediating the chronic shortage of historically underrepresented investigators in scientific research. After presenting the magnitude of the problem and a rationale for enhancing diversity of the biomedical research workforce, we identify a number of potential reasons and challenges for the shortage of minority investigators. Aspects of the mentoring process, together with ten key suggestions, are discussed as the backdrop for the supplement papers that follow (dealing with mentoring principles, challenges, and mentoringrelated issues on mentee, mentor, mentee-mentor relationship, and programs). By identifying these realities we hope to: (1) promote greater discussions of these challenges in academic institutions and settings; (2) suggest meaningful strategies to address these challenges; and (3) foster a national discussion about the long-term investment necessary for permanent change, as there are no easy 'fixes' for these challenges.