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Environmental influences on biological risk for psychosis are increasingly recognized but not well understood. While exposure to childhood maltreatment is well known to increase risk of psychosis in adulthood, the effects of childhood maltreatment on the brain and stress-related biological systems has been relatively understudied in these disorders. Here, I describe a series of investigations in which the effects of childhood maltreatment form a critical element in the attempt to biologically parse psychotic disorders (schizophrenia, schizoaffective disorder, and bipolar-I disorder) within the framework espoused by the Research Domain Criteria (RDoC). Our clinical research demonstrates increased deficits in social cognition in cross-disorder clinical cases exposed to childhood maltreatment (i.e., regardless of diagnosis), alongside reductions of grey matter concentration in the temporo-parietal/occipital junction, and reduced functional connectivity of the amygdala with frontal and temporal regions during affect processing. We have also seen statistical interactions between maltreatment exposure and common genetic variants affecting the brain (e.g., hippocampal volume) and cognition in a national schizophrenia sample. These findings are augmented by new epidemiological research demonstrating the pervasive effects of childhood maltreatment across developmental domains of function at age 5 years, in a longitudinal population study of children in the New South Wales Child Development Study (NSW-CDS), for which adolescent outcomes are forthcoming. Implications for future research will be discussed.