Ever since Edward Jenner injected a village boy with pus from a cowpox pustule on the theory that doing so would protect the lad from smallpox—a deadlier disease by far—research with human subjects has formed the bridge between basic science breakthroughs in the lab and advances in patient care. Today, a larger portion of federal research dollars than ever before is dedicated to clinical and translational research. This month’s issue explores the challenges of protecting human-research subjects and assuring the scientific integrity of research outcomes.