Schizophrenia is a mental disorder of a multifactorial origin that involves both genetic and environmental influences. Technological innovations and recent discoveries in genetics have advanced our understanding of the genetic structure of the disease. However, even with the high number of risk variants identified, heritability estimates suggest an important contribution of nongenetic factors. There are many environmental risk factors known to be associated with the development of schizophrenia. These include parental age, season of birth, maternal infections, obstetric complications, residential status, adverse events at early childhood, and substance abuse. Despite all the progress in the field, we still have a limited understanding of the mechanisms whereby gene–environment interaction works to cause schizophrenia. In this chapter we offer an analysis of currently available animal models of gene–environment interaction in schizophrenia and propose ways to facilitate development of new experimental approaches to the complex mechanisms behind this disorder.