Autism is a heterogeneous neurodevelopmental disorder. The etiology of autism remains unknown although both genetic and environmental factors are likely to be involved. These factors disrupt the course of normal brain development from the cellular to the gross anatomical levels. The Reelin, gamma-aminobutyric acid (GABA), and fragile X mental retardation protein (FMRP)-metabotropic glutamate receptor 5 (mGluR5) signaling systems play important roles during the development of the nervous system. Disruption of these pathways is likely to lead to altered synaptic transmission and, ultimately, the cognitive and behavioral deficits associated with autism. This chapter describes each of these signaling systems and summarizes the current evidence that link them to autism. Therapies that target molecules in these signaling systems may provide new means of treating the core symptoms of autism.