The elucidation of the causes of complex diseases pivots on understanding the interaction between biological (genetic) and environmental factors that give rise to disease risk. The modest effects of genetic factors in complex diseases supports the need for large-scale studies of high-quality human biological materials, paired with detailed clinical data, to adequately detect these effects. To this end, biobanks or biorepositories have been developed around the world, by public and private entities alike, to provide researchers the opportunity to study collections of human biospecimens annotated with clinical and other health-related measurements. It has been estimated that more than 270 million tissue samples are stored in the U.S., expanding at a rate of approximately 20 million samples annually. In this chapter, we discuss several ethical, legal, and social issues that have been raised surrounding biobanks, including recruitment of vulnerable populations, informed consent, data disclosure to participants, intellectual property, and privacy and security. Throughout the chapter, we will highlight experiences of national biobanks in Iceland, the U.K., Sweden, and Estonia, and the proposal for a U.S. population cohort study. The dependence on public participation requires clear and transparent policies developed through inclusive processes.