Ethnic minorities have disproportionately high mortality rates due to cancer, and biomedical research suggests evidence of racial/ethnic differences in drug treatment response, drug metabolism, and a predisposition to certain cancers. Participation in oncology treatment clinical trials offers the best possible hope for improving cancer prevention, early detection and treatment and for reducing disparate outcomes across certain racial and ethnic groups. However, multiple and varied psychological and social barriers currently prevent proportional representation of racial and ethnic minority groups in clinical trials. Utilizing a Social Ecological perspective, this paper presents a multi-level categorization of psychosocial barriers to participation in oncology clinical trials among racial and ethnic minority groups. These barriers can be effectively conceptualized as Intrapersonal Barriers (i.e. attitudes, beliefs about cancer), Interpersonal Barriers (i.e. language, power differentials in the patient-doctor relationship communication), Environmental Barriers (i.e. socio-economic status, low health literacy, lack of knowledge about clinical trials, health care access), Community Barriers (i.e. lack of community leader influence), and Institutional Barriers (i.e. underdeveloped health system infrastructure to promote clinical trials). Ultimately, individual patients make the decision whether to participate in clinical trials. Thus, diverse representation in clinical trials partially depends upon the enhancement of perceptions about the benefits of participation in clinical trials. The Health Belief Model guides an understanding of how psychosocial barriers impact the person in their environment such that ecological factors influence individual perceptions of risk, severity and overall threat of clinical trial participation. Furthermore, cultural explanatory theories contribute to an understanding of unique Socio-Cultural Barriers to clinical trials participation (i.e. feelings of mistrust or fear based on past historical injustices, beliefs about Western medicine, religion, culturally-influenced gender roles). Social work research can inform the development of ethnically and culturally appropriate interventions at micro-, meso- and macro-levels to encourage ethnic minority clients' participation in clinical trials. On a micro-level, social workers can help individual's regain trust and confidence in medical and research institutions. Participation is likely to stimulate the development of cross-cultural clinical trial education and promotional interventions to be tested, which can capture the needs of diverse groups. On a meso-level, social work practitioners and researchers can align with laypersons and community leaders in establishing community-based, collaborative efforts with healthcare institutions to reduce accessibility problems for participants. On a macro-level, social work research on clinical trials participation can inform policy makers about how to fund and develop institutional infrastructures that will support the inclusion of racial and ethnic minorities in investigations of multi-factorial influences (i.e. genetic, dietary, and environmental) on cancer prevention, etiology, and treatment efficacy outcomes. Social workers can play a critical role in addressing psychosocial barriers to oncology clinical treatment trials, thus maintaining one of the primary goals of Healthy People 2010 (U.S. Department of Health and Human Services, 2000) -reducing ethnic health disparities.