Maternal immune activation (MIA) is an important environmental risk factor for schizophrenia. Among various modes of MIA, modeling maternal viral infection by injecting pregnant rodents with the double-stranded RNA polyinosine-polycytidylic yields offspring with strong face, construct, and predictive validity for symptoms related to schizophrenia. The MIA model is a powerful tool for investigating molecular mechanisms underlying the etiopathogenesis of schizophrenia-related features and for uncovering key molecular targets for intervention. Here we introduce the epidemiological bases for the MIA model and present important findings on both prenatal and postnatal variations of the polyinosine-polycytidylic approach. We further describe applications of the MIA model to studies of gene–environment and environment–environment interactions in schizophrenia. Finally, we discuss the MIA risk factor in the context of increasing evidence that immune dysregulation contributes to the manifestation of schizophrenia-related symptoms.