A significant variability is observed among patients in response to antipsychotics, and is caused by a variety of factors. This review summarizes the available knowledge of associations between pharmacogenetics and drug response in schizophrenia. The multifactorial etiology of schizophrenia makes it a complex interaction of symptoms. Adopting a pharmacogenomics approach represents a unique opportunity for the prediction of response to antipsychotic drugs by investigating genes implicated with specific symptoms and side effects. A network model of the interaction/crosstalk between the neurotransmitter signaling systems is presented to emphasize the importance of the genes associated with the molecular mechanisms of the disease and drug response. These genes may serve as potential susceptibility genes and drug targets for schizophrenia. The crucial point for the identification of a significant biologic marker(s) will include not only the experimental validation of the genes involved in the neurotransmitter signaling systems, but also the availability of large exactly comparable phenotyped patients samples. Coupling our knowledge of genetic polymorphisms with clinical response data promises a bright future for rapid advances in personalized medicine.