The 2016 Albert Lasker Basic Medical Research Award honors three physician-scientists for their discovery of the pathway by which cells from human and most animals sense and adapt to changes in oxygen availability, a process that is essential for survival. Scientists had long appreciated that the success of today’s dominant life forms hinges on oxygen, yet little was known about their responses to it. William G. Kaelin, Jr. (Dana-Farber Cancer Institute/Harvard Medical School),Peter J. Ratcliffe (University of Oxford/Francis Crick Institute), and Gregg L. Semenza (Johns Hopkins University School of Medicine) illuminated the core molecular events that explain how almost all multicellular animals tune their physiology to cope with varying quantities of the life-sustaining element, thus exposing a unique signaling scheme.