Liver or renal failures are common medical conditions, and many patients have comorbid psychiatric disorders. Liver and kidney have significant roles in the pharmacokinetics of drugs including the mechanisms of absorption, distribution, metabolism or excretion. The liver is the primary site for metabolism of psychotropic drugs. The processing and elimination of drugs from the body occurs through two phases of metabolism: phase 1 reactions, during which CYP 450 enzymes convert the parent compound to metabolites through processes of oxidation, reduction, or hydrolysis and phase two reactions, which couple the metabolites with endogenous substances rendering them more water-soluble for excretion from the body. Regarding antidepressant metabolism, the CYP 2D6 and CYP 3A4 systems may be the two most important metabolic pathways, as most psychotropic drugs are eliminated via these pathways. Liver failure affects basic elements of medication pharmacokinetics, from absorption to metabolism, distribution to elimination, changing drug levels, duration of action, and efficacy. Additionally, physiological models of hepatic drug elimination have emphasized the importance of physiological variables such as hepatic blood şow, protein binding and intrinsic clearance of the liver on hepatic drug elimination. Dose adjustment of psychotropic drugs in patients with liver disease may be important as most of these drugs are predominantly eliminated by the liver and many of them are associated with dose-dependent adverse reactions. Following the administration of a drug to a patient with hepatic impairment, careful monitoring of the patient and also monitoring of plasma or blood drug concentrations remain important considerations. The kidney is a primary route of drug elimination; abnormal kidney function is predicted to alter the pharmacokinetics of agents metabolized and/or excreted predominantly through this route. In renal failure, there is a general slowing of chemical reduction and of hydrolysis, but there are normal rates of glucuronidation, microsomal oxidation, and sulfate conjugation. Drug metabolites that are pharmacologically active may be retained in patients with renal insufficiency and may cause adverse effects. Very few drugs are excreted from the body unchanged in the urine; most are metabolized within the body to less lipid-soluble compounds that are excreted by the kidneys. So that few drugs are contraindicated with end stage organ dysfunction, but many require dose adjustment and caution. Guiding principles include, but are not limited to, slow titration of doses, low-dose treatment initiation, and careful monitoring of clinical response. Psychiatric consultants need to be aware of the presence of comorbid renal, liver and psychiatric disorders, and they should be knowledgeable about the use of psychotropic medications in this situation. Disease-related changes in pharmacokinetics and pharmacodynamics, as well as vulnerability to side effects, polypharmacy, and potential drug interactions are all important considerations.