Although a number of typical and atypical antipsychotics (AP) have been discovered and used in psychiatric clinical practice the variability in response to AP is quite high. This variability is partially explained by a genetic heterogeneity of schizophrenia and metabolism of AP. The standard prescribed antipsychotic daily dose is not always optimal. Genetic variability of biotransformation and bioavailability of AP may significantly influence on therapeutic effect and tolerability. The aim of the study was to perform literature review of studies evaluating the correlation of CYP2D6 genetic polymorphisms and AP pharmacokinetics, effectiveness and safety. Most pharmacokinetics studies show high positive significant correlation between CYP2D6 metabolic activity, determined by CYP2D6 polymorphisms genotyping and AP pharmacokinetic parameters (AUC, elimination half-life, clearance etc.). However the majority of studies were failed to demonstrate significant correlation between CYP2D6 polymorphisms and AP effectiveness mainly due to inadequate number of patient, heterogeneous cohorts, different AP and effectiveness criteria used. Prospective studies with balanced comparison groups and large retrospective studies showed significant correlation between CYP2D6 metabolic status and the frequency of AP induced AEs (parkinsonism and tardive dyskinesia). To better assess the influence of CYP2D6 genetic polymorphisms on AP effectiveness and safety in clinical routine large prospective well designed clinical studies are needed.