Autism spectrum disorders (ASD) and schizophrenia were separated into different diagnostic categories in the late 1970's (DSM-III) having previously been considered as related diagnostic entities. Since then, several lines of evidence have indicated that these disorders show clinical and cognitive overlaps as well as some common neurobiological characteristics. Furthermore, there is a group of patients presenting with ASD and psychotic experiences who pose particular diagnostic and management challenges and may represent a subgroup of ASD more closely linked to psychosis. Evidence from a study of the first empirically derived classification of children with ASD in relation to psychosis based on three underlying symptom dimensions, anxiety, social deficits and thought disorder, will be presented. Further phenomenological, genetic and neuroimaging research on the clinical boundaries and overlapping pathophysiology of ASD and psychosis may help better define their relationship and lead to more effective interventions. Understanding this relationship will also provide a framework of working with patients with mixed clinical presentations.