Elderly patients suffering from mental diseases are frequently comedicated with different psychopharmacological agents including antidepressants, antipsychotics, anxiolytics, hypnotics, cognitive enhancers and anticonvulsants used as mood stabilizers. In addition, somatic drugs are co-prescribed for the treatment of other concomitant diseases. This situation increases the risk for pharmacokinetic interactions with pharmacodynamic consequences. This population is particularly sensitive to adverse effects due to an impaired homeostatic reserve. Moreover, drug absorption, distribution, metabolism and elimination (ADME) may be altered in the elderly. However, studies in very old patients (> 80y) are often lacking. Therefore, treatment needs to be carefully and individually tailored. Therapeutic drug monitoring may be a useful tool to optimise treatment, as some “classical” indications apply for this population: Lack of compliance, adverse effects despite the use of generally recommended doses, suspected drug interactions, combination treatment with a drug known for its interaction potential, patients with pharmacokinetically relevant comorbidities (hepatic or renal insufficiency, cardiovascular disease). The increasing knowledge on the role of cytochrome P-450 isozymes in the metabolism of drugs and their interaction potential has fortunately led to a situation, which allows, to some extent, predicting risks for adverse effects after introducing a polymedication.