The health and well-being of all individuals, independent of race, ethnicity, or gender, is a significant public health concern. Despite many improvements in the status of minority health, African American males continue to have the highest age-adjusted mortality rate of any race-sex group in the United States. Such disparities are accounted for by deaths from a number of diseases such as diabetes, human immunodeficiency virus (HIV), cancer, and cardiovascular disease, as well as by many historical and present social and cultural constructs that present as obstacles to better health outcomes. Distrust of the medical community, inadequate education, low socioeconomic status, social deprivation, and underutilized primary health care services all contribute to disproportionate health and health care outcomes among African Americans compared to their Caucasian counterparts. Results of clinical research on diseases that disproportionately affect African American males are often limited in their reliability due to common sampling errors existing in the majority of biomedical research studies and clinical trials. There are many reasons for underrepresentation of African American males in clinical trials, including their common recollection and interpretation of relevant historical of biomedical events where minorities were abused or exposed to racial discrimination or racist provocation. In addition, African American males continue to be less educated and more disenfranchised from the majority in society than Caucasian males and females and their African American female counterparts. As such, understanding their perceptions, even in early developmental years, about health and obstacles to involvement in research is important. In an effort to understand perspectives about their level of participation, motivation for participation, impact of education, and engagement in research, this study was designed to explore factors that impact their willingness to participate. Our research suggests that: (1) African American males across all ages are willing to participate in several types of research studies, even those that require human samples; (2) their level of participation is significantly influenced by education level; and (3) their decision to participate in research studies is motivated by civic duty, monetary compensation, and whether they or a relative has had the disease of interest. However, African American males, across all age groups, continue to report a lack of trust as a primary reason for their unwillingness to participate in biomedical research. There is an ongoing need to continue to seek advice, improve communication, and design research studies that garner trust and improve participation among African American males as a targeted underrepresented population. Such communication and dialogues should occur at all age levels of research development to assess. current attitudes and behaviors of African American males around participation.