Clinical research requires representation of racially and ethnically diverse participants to accurately represent the general population. Overall life expectancy of African Americans is shorter than that of the general U.S. population. Compared with the other ethnic groups in the United States, African Americans have higher rates of hypertension, stroke, obesity, and diabetes, and higher rates of mortality related to stroke and cancer. Although many health disparities exist among African Americans, they are well underrepresented in clinical research. This article provides an overview of barriers that may influence participation in clinical research among African Americans. Issues of trust, experimentation, communication, and logistics are the most commonly identified barriers. The barriers and facilitators identified in this review may be useful in the development and implementation of recruitment and research strategies that are culturally sensitive and that may enhance trust and willingness to participate among African Americans.