Although autism was first formally described many decades ago by Kanner (1943) and Asperger (1944), research on the disorder in the U.S. remained scarce until the 1990s. At that time, researchers developed new neuroscientific methods that could be applied to investigations of the psychological and biological underpinnings of autism, including genomics, eye-movement tracking, and electrophysiology. As a result, researchers and practitioners are gaining greater understanding of the disorder. The complexity and enigma of autism still remain, particularly its alterations of a wide and seemingly unrelated group of behavioral symptoms that have no obvious correspondence to a single biological function. In addition, the disorder occasionally includes perceptual advantages. To address the three elements of the enigma, we suggest that the diversity of symptoms can be understood as a consequence of a widespread neural systems disorder; the link to a biological substrate is illuminated by brain imaging; and a perturbation of the cortical system can have both negative and positive impacts on functioning.