Recruitment of African-Americans, particularly men in clinical and prevention studies, has not been successful and retention is a major challenge. The paper examines the impact of the Tuskegee Study on research in the 21st century and its effect on recruitment of African-Americans into medical studies. A total of 6 focus groups were conducted among male participants diagnosed with prostate cancer to elicit responses regarding factors influencing participation into prospective studies and trials. Sessions were transcribed and analyzed using content analysis. Echoes of the Tuskegee Public Health Study legacy was a major concern voiced by participants throughout the focus group process. Participants recognize the importance and benefit of research, however the potential for unethical practices continue to linger in the minds of participants. Attitudes and beliefs toward research and the stigma associated with the Tuskegee Public Health Study must also be addressed to increase enrollment of African-Americans in medical studies.