To obtain optimal results than pharmacotherapy, therapy with the purpose to make personalized methods used has been increasing in recent years. These methods relates to detecting changes in pharmacokinetics and pharmacodynamics. P glycoprotein (P-gp) and enzyme systems (CYP) responsible for drug metabolism due to genetic factors are changes in drug pharmacokinetics. The P-glycoprotein multi drug transporter (P-gp, ABCB1) is a member of the ABC (ATP-binding cassette) super family. In vitro and in vivo studies have demonstrated that P-gp plays a significant role in drug absorption and disposition because of its localization, P-gp appears to have a greater impact on limiting cellular uptake of drugs from blood circulation into brain and from intestinal lumen into epithelial cells than on enhancing the excretion of drugs out of hepatocytes and renal tubules into the adjacent luminal space. For instance, induction of the intestinal P-gp activity can cause reduced bioavailability of orally administered drugs and decreased therapeutic efficacy. On the other hand, the inhibition of the intestinal P-gp activity can lead to increased bioavailability, thus leading to an increased risk of adverse side effects. The brain uptake of the majority of antidepressants and antipsychotics, as well as many other psychotropic drugs and endogenous compounds are hampered by the activity of P-gp. In this presentation, we discuss the current state of knowledge concerning the role of P-gp on pharmacokinetics of psychiatric drugs and the impact of modulation of P-gp on major psychiatric disorders. Relevant issues in reference to the function of P-gp and other efşux pumps in the blood-brain barrier related to mood disorders and schizophrenia are addressed, such as a possible role of P-gp as a susceptibility factor in depressive disorders and psychotic disorders.