It is well documented that African American/Black and Hispanic individuals are underrepresented in biomedical research in the United States (U.S.), and leaders in the field have called for the proportional representation of varied populations in biomedical studies as a matter of social justice, economics, and science. Yet achieving appropriate representation is particularly challenging for health conditions that are highly stigmatized such as HIV/AIDS. African American/Black, and Hispanic individuals, referred to here as “people of color,” are greatly overrepresented among the 1.2 million persons living with HIV/AIDS in the United States. Despite this, people of color are substantially underrepresented in AIDS clinical trials. AIDS clinical trials are research studies to evaluate the safety and effectiveness of promising new treatments for HIV and AIDS and for the complications of HIV/AIDS, among human volunteers. As such, AIDS clinical trials are critical to the development of new medications and treatment regimens. The underrepresentation of people of color in AIDS clinical trials has been criticized on a number of levels. Of primary concern, underrepresentation may limit the generalizability of research findings to the populations most affected by HIV/AIDS. This has led to serious concerns about the precision of estimates of clinical efficacy and adverse effects of many treatments for HIV/AIDS among these populations. The reasons for the underrepresentation of people of color are complex and multifaceted. First, people of color experience serious emotional and attitudinal barriers to AIDS clinical trials such as fear and distrust of medical research. These experiences of fear and distrust are grounded largely in the well-known history of abuse of individuals of color by medical research institutions, and are complicated by current experiences of exclusion and discrimination in health care settings and the larger society, often referred to as structural racism or structural violence. In addition, people of color experience barriers to AIDS clinical trials at the level of social networks, such as social norms that do not support engagement in medical research and preferences for alternative therapies. People of color living with HIV/AIDS experience a number of structural barriers to clinical trials, such as difficulty accessing and navigating the trials system, which is often unfamiliar and daunting. Further, most health care providers are not well positioned to help people of color overcome these serious barriers to AIDS clinical trials in the context of a short medical appointment, and therefore are less likely to refer them to trials compared to their White peers. Last, some studies suggest that the trials’ inclusion and exclusion criteria exclude a greater proportion of people of color than White participants. Social/behavioral interventions that directly address the historical and contextual factors underlying the underrepresentation of people of color in AIDS clinical trials, build motivation and capability to access trials, and offer repeated access to screening for trials, hold promise for eliminating this racial/ethnic disparity. Further, modifications to study inclusion criteria will be needed to increase the proportion of people of color who enroll in AIDS clinical trials.