The relatively low participation of African Americans in phase III clinical trials has raised concerns about the appropriateness of generalizing study results to African American populations. If African American enrollment in clinical trials continues to be low, the society may continue to see disparities in the treatment of diseases as well as unanswered questions as to why the population fares less than others when diagnosed with certain diseases such as cancer and diabetes. Additionally, more clinical trials are needed to explicitly monitor the difference in outcomes across different populations. This article discusses the various reasons why African American patient recruitment and participation is sub-optimal; the critical role of clinical trials in therapies; recommendations by important authorities; and a new practice model (Collaborative Care Model) as an innovative strategy to augment participation rates of African Americans [and other minorities] in clinical trials.