The blood-brain barrier must not be regarded as a purely passive wall opposing low permeability to undesirable compounds circulating in blood. It limits the access of molecules to brain tissue by a joint interplay of cerebro-spinal fluid turnover and selective uptake and expulsion of compounds through active drug carriers. The inhibition of such transporters can increase brain penetration of substrates leading to drug interactions with neuropsychiatric manifestations; it can also be exploited to increase brain and CSF concentrations of anti-infective, anti-neoplastic or psychotropic agents. Genetic polymorphisms affecting transporters may modulate the brain exposure to drugs in selected individuals. Such observations improve our understanding of a key mechanism governing clinical neuro-psychopharmacology.