In the last years efflux transporters, as for example P-glycoprotein, have been shown to play an important role in the regulation of the uptake of drugs in the central nervous system. These transporters are expressed constitutively in the brain capillary endothelial cells which form the brain-blood barrier, but their expression or activity could be inhibited or induced by other compounds or could be modified under pathological conditions. Some antipsychotics (amisulpride, chlorpromazine, fluphenazine, haloperidol, olanzapine, pimozide, prometazine, quetiapine, risperidone, trifluoperazine), antidepressants (amitriptiline, doxepine, nortriptiline, venlafaxine), and antiepileptics (felbamate, gabapentin, lamotrigine, phenobarbital and topiramate) are P-glycoprotein substrates. Interactions that could take place at the P-glycoprotein level may explain some cases of resistance in polimedicated patients. Other factors, yet unknown, could induce the expression of this transporter and therefore decrease the uptake of psychotropic drugs in the central nervous system, affecting their efficacy.