Display omitted •Altered social behavior is a pathological trait of autism spectrum disorder (ASD).•In mice, mutations in ASD genes result in altered social behavior.•Mouse models are a crucial tool to develop novel treatments for ASD. Social behavior is evolutionary conserved, and is thought to be evolved since it increased reproductive and survival fitness of living species. In humans, disturbances of social behavior are a peculiar pathological trait of neurodevelopmental disorders, namely autism spectrum disorder (ASD). ASD is defined by deficits in two core domains (social interaction/communication and repetitive/restrictive behaviors), which emerge during early postnatal development. ASD has a strong genetic component: copy number variations, de novo and familial mutations, as well as epigenetic modifications have been reported in a huge number of genes. Recent studies in mice demonstrate that mutations in a wide variety of ASD-associated genes can cause neurodevelopmental defects, which subsequently result in social behavior disturbances during early postnatal age and adulthood. From these studies, it clearly emerges that functionally interrelated cellular mechanisms underlie social behavior and its disturbances in ASD. Indeed, most of ASD-associated genes control neuronal differentiation and migration, growth of neuronal connections and synaptic function. Here we will present the recent advances in understanding the genetic determinants of social behavior, as they emerge from the study of ASD mouse models, and discuss the importance of these studies for the development of novel therapeutic approaches to overcome social disturbances in ASD.