Autism is a lifelong developmental disorder that is associated with severe difficulties with ''theory-of-mind''--the understanding that others' behaviors are motivated by internal mental states. Here, we raise the possibility that research examining the neural bases of theory-of-mind reasoning has the potential to inform researchers about the elusive functional neural impairments associated with autism. Evidence from our lab and others' suggests that theory-of-mind reasoning may be fractionated into at least two functionally and anatomically distinct neural circuits. Specifically, the ability to decode others' mental states from observable cues (such as facial expressions) may rely on contributions from the orbitofrontal/medial temporal circuit within the right hemisphere. In contrast, the ability to reason about others' mental states may rely left medial frontal regions. We conclude by reviewing evidence suggesting that the developmental roots of autism might lie in abnormal functioning of the orbitofrontal/medial temporal circuit which may, in turn, underlie the abnormal development of social-cognitive skills among individuals with autism.