Disrupted-in-Schizophrenia 1 (DISC1 ) is a strong candidate gene for schizophrenia and major mental disorders. After its discovery in the Scottish chromosomal translocation, DISC1 has gained considerable attention in neuropsychiatric research. Recent studies have implicated DISC1 in fundamental processes of neurodevelopment and adulthood neuroplasticity. To get more insights into the functions of DISC1 in vivo, several mouse DISC1 models have been generated based on different approaches, including constitutive and inducible over-expression of different fragments of DISC1, targeted mutagenesis, and viral vector knockdown. Each model has provided important information regarding DISC1 functions and helped in elucidating the molecular pathways underlying behavioral disorders. The existing models also serve as valuable tools to address complex issues of the pathogenesis of schizophrenia, including gene–gene and gene–environment interactions. Here, we critically overview current DISC1 mouse models. Future directions in DISC1 mouse models and alternative approaches are discussed.