This chapter focuses on two specific populations of individuals often vulnerable in the conduct of research: children and prisoners. With children, prisoners, and other vulnerable populations, the challenge is to find the right balance between protection from abuse and the need to grant vulnerable populations access to participation in research. Necessary protections have two components: fair subject selection, and the specific care required to minimize wrongs to vulnerable persons once they are enrolled in research. As a group, prisoners are vulnerable due to their particular situation: being detained and therefore being deprived of the freedom to move freely. Several prison-related factors are relevant for ethical considerations about research involving prisoners. Studies designed to address health problems specific to a vulnerable population are needed to improve care for this very population, and often cannot be conducted on others.