Liver, a major metabolic organ in the body, is unique and has many functions other than biotransformation of drugs. Commonly performed liver function tests do not accurately quantitate the degree of metabolic dysfunction of the liver. Even specific tests such as lidocaine MEG-X test and antipyrine or indocyanine green clearance tests of drug metabolism do not accurately assess or predict the pharmacokinetic changes of drugs in patients with liver disease. Some drugs undergo phase I reactions that may be significantly affected by hepatocellular disease but not by cholestatic disease. Factors other than intrinsic metabolic insufficiency due to liver disease such as changes in liver blood flow, serum albumin, portosystemic shunts, or pharmacodynamic sensitivity also play a significant part in drug metabolism and their effect. Further, considerable interindividual variability exists in response to many drugs in patients with liver disease. Ultimately, it is difficult to consistently predict clinical effects of any given drug in patients with liver disease. Therefore, careful titration of drug to its clinical effects and continued vigilance and monitoring for its side effects are critical in any patient with liver disease.