Our understanding of autism risk factors has grown exponentially in the past few years. Cellular and animal models based upon some of these risk factors are providing clues to the underlying neurobiology. The most advanced work has emerged in rare genetic syndromes that often include autism symptoms: tuberous sclerosis, fragile X, Rett, and Phelan-McDermid syndromes. In each syndrome, hypothesized neurobiological mechanisms are now being tested in human treatment studies. This panel will outline insights from specific studies in these rare syndromes, but it will also provide a perspective on the pathway from risk factor to mechanism to potential treatment. Presentations in this panel will highlight (1) candid evaluations of model systems for dissecting the biology of neurodevelopmental disorders and testing potential treatments; and (2) perspectives on assessing potential benefits and risks in the context of developmental change and the placebo effect. These rare syndromes offer the first opportunity to test treatments based upon an understanding of neurobiological mechanisms. By finding treatments that show benefit in these rare syndromes, we may also gain an understanding of how to develop and test treatments in neurodevelopmental disorders more broadly. Potentially, some treatments may even benefit a larger subgroup of children with ASD.