Strategic and legislative efforts to catalyse pharmaceutical innovation may be hampered by a lack of consensus over what characterizes an innovative drug. To help clarify this issue, we conducted an extensive survey on transformative drug development, involving ∼180 expert physicians based at 30 leading US academic medical centres, covering 15 medical specialties. In an iterative Delphi process, the survey participants narrowed a list of all new drugs approved in their fields in the past 25 years and reached consensus over those that they considered to be most transformative, which are presented in this article. Participants were also asked how various factors affected their opinion; they most often invoked the effectiveness and superiority of the drugs over existing alternatives when identifying transformative drug innovation.