During Stuart Orkin’s training as a physician-scientist, he decided to focus on pediatric blood disorders as an area where disease genetics could connect directly to scientific investigations. His work in this field ultimately identified the genetic mutations responsible for thalassemia and chronic granulomatous disease. Recently, his focus has shifted toward singling out hematopoietic targets that can be exploited to treat hematological disorders, including leukemia and sickle cell disease. In this issue of the JCI, Editor at Large Ushma Neill interviews Dr. Orkin to discuss his path toward medicine and scientific research as well as the stories behind these highlights of his research career.