Older incarcerated individuals comprise the fastest growing demographic in the US prison system. Unhealthy lifestyles among incarcerated individuals and inadequate health care lead to earlier onset and more rapid progression of many chronic conditions that are prevalent among community-living older adults. There are limited peer-reviewed epidemiologic data in this area; however, there is growing interest in identifying strategies for housing aging incarcerated individuals, delivering appropriate health care in prisons, and coordinating after-release health care. In this systematic review, we summarize the epidemiologic evidence of the health challenges facing the aging US prison population. Our comprehensive literature search focused on health outcomes, including diseases, comorbid conditions, mental health, cognition, and mobility. From 12,486 articles identified from the literature search, we reviewed 21 studies published between 2007 and 2017. All the studies were observational and cross-sectional, and most (n = 17) were based on regional samples. Sample sizes varied widely, ranging from 25 to 14,499 incarcerated people (median, 258). In general, compared with their younger counterparts, older incarcerated individuals reported high rates of diabetes mellitus, cardiovascular conditions, and liver disease. Mental health problems were common, especially anxiety, fear of desire for death or suicide, and depression. Activities of daily living were challenging for up to one-fifth of the population. We found no empirical data on cognition among older incarcerated individuals. The findings of this review reveal few empirical data in this area and highlight the need for new data to drive policy and practice patterns that address critical health issues related to the aging prison population.