The purely descriptive definition of autism introduced by the DSM III in 1980 marked a departure from previous DSM editions, which mixed phenomenological descriptions with psychoanalytic theories of etiology. This provided a blank slate upon which a variety of novel theories emerged to conceptualize autism and its treatment in the following four decades. In this article we examine the contribution of these different theoretical orientations with a focus on their impact on research and practice, areas of overlap and conflict between current theories, and their relevance in the context of the evolving landscape of scientific knowledge and societal views of autism.