There is no generally accepted theory of humor in psychology. In the context of linguistic work on jokes, there are a few formal theories. There is very little research on humor in clinical contexts, and even less in neuroscience. What about humor makes it so difficult to study scientifically, and especially from the perspective of mechanistic explanatory frameworks embraced in contemporary neuroscience? This chapter explores the idea that current research on humor in the neurosciences suffers because prominent theories of humor in psychology and linguistics were first articulated in the terms provided by cognitive schema theories, which typically de-emphasize the social and emotional aspects of humor, and expressly disavow commitments regarding neurological implementation. When investigations pursued by neuroscientists have been successful, it appears that they are focused on the mechanisms of amusement in ways designed to bridge the gap between humor’s cognitive and neurophysiological dimensions.