The study of gene–environment interaction (G × E) constitutes an area of significant social and clinical significance. Different types of research study designs are being used to investigate the contribution of G × E to psychopathology, although the term G × E has also been used and interpreted in different ways. Despite mixed evidence that G × E contributes to psychopathology, some promising and consistent findings are emerging. Evidence is reviewed in relation to depression, antisocial behavior, schizophrenia, and attention-deficit/hyperactivity disorder. Although findings from various research designs have different meaning, interestingly much of the evidence with regard to the contribution of G × E that has arisen from twin and adoption studies has been for antisocial behavior and depression. It is for these same forms of psychopathology that molecular genetic evidence of G × E has also been most convincing. Finally, current and anticipated methodological challenges and implications for future research in this area are considered.