Incarcerated individuals, over 95% of whom are eventually released, experience high burdens of chronic disease and behavioral health and social risk factors. Understanding the health needs of this population is critical to ensuring that general medicine physicians in prisons and in the community are adequately prepared to meet those needs. However, people in prison are significantly underrepresented in health research. In response to historical exploitation of prisoners in medical experimentation, federal guidelines appropriately require additional oversight for, and limit the scope of, research in prisons. Yet, according to a 2006 Institute of Medicine report, these requirements have produced inconsistent local regulations that often limit opportunities for incarcerated individuals to participate in research, and can slow the development of innovative medical interventions to improve their health. In this article, we describe the historical context surrounding regulations on research involving individuals in prison, the harms that can arise from excessive limitations to research in such settings, and the benefits of greater access to ethically conducted research in prison. We conclude with recommended actions that can be taken by general medicine researchers, correctional leaders, and policymakers to achieve consistent access to health research for incarcerated populations.