Commemorating the 40th anniversary of the Diagnostic and Statistical Manual (DSM) III, the purpose of this commentary is to describe school-based and school-relevant interventions and instructional approaches for children and youth with autism that have been developed and employed during that time period. The commentary begins with a brief description of foundational research that provides an historical context. Research themes shaped by science, ethics, social policy, and the changes in the DSM provide an organization for describing the evolution of intervention and instructional practices over the four previous decades. The commentary concludes with a discussion of school-contextual variables that influence implementation and the promise of the "iSciences" for closing the research to practice gap in the future.