Transplant specialists face two critical paradoxes. First, their success has spurred demand for their services and expertise, yet the supply of organs is scarce. Second, to help their patients, physicians need a voluntary sacrifice from another human being. In this issue of the AMA Journal of Ethics, we illuminate key concepts professionals and patients in transplant medicine: consent, extended criteria organs, regulatory oversight, and donor incentives. Authors in this issue are transplant ethicists and clinicians grappling with ethical questions and possibilities at the boundaries of surgical knowledge.