Schizophrenia and autism have been linked since their earliest descriptions. Both are disorders of cerebral specialization originating in the embryonic period. Genetic, molecular, and cytologic research highlights a variety of shared contributory mechanisms that may lead to patterns of abnormal connectivity arising from altered development and topology. Overt behavioral pathology likely emerges during or after neurosensitive periods in which resource demands overwhelm system resources and the individual's ability to compensate using interregional activation fails. We are at the threshold of being able to chart autism and schizophrenia from the inside out. In so doing, the door is opened to the consideration of new therapeutics that are developed based upon molecular, synaptic, and systems targets common to both disorders.