The greatest challenge of schizophrenia research remains the identification of the multiple, common, interacting, and moderately penetrant mutations that interfere with the highly complex function of human brain and result to this devastating disease. The inaccessibility of the human central nervous system to experimental manipulations and the paramount difficulties in identifying genes for schizophrenia has led researchers to generate mouse models for candidate genes using gene-targeting approaches. Although such mouse models have proven very useful in deciphering the causes of several diseases of the central nervous system (such as neurodegenerative diseases), their use in dissecting the biology of schizophrenia is still in its infancy. We argue that progress in this direction depends highly on progress in human genetic studies and requires careful and critical interpretation of the accumulating data.