We are a multidisciplinary collaborative made up of bioethicists, social scientists, clinicians, and lawyers whose work focuses on the ethical challenges posed by a networked approach to biorepositories. Like many, we have been concerned that our human research regulations had become woefully out of date. While the interventional, hypothesis-driven research envisioned by the 1991 Common Rule remains important, contemporary research increasingly depends on the collection of samples and data for unspecified future research. Over the past decade, large collections of biological materials for research have grown in complexity and scope, creating interinstitutional, national, and international networks. These networks of biorepositories also are embedded in research pathways that leverage learning health systems, big data analytics, and sophisticated health informatics approaches.