Patients with liver disease often show unusual responses to "standard" doses of drugs. Increased variability of response to drugs which are predominantly eliminated by the liver is mainly due to altered pharmacokinetics in the presence of hepatic dysfunction. The possible prediction of abnormal pharmacokinetics in hepatic disease requires a knowledge of the pharmacokinetic characteristics of a particular drug in healthy subjects and of the major pathophysiologic alterations which occur in a given form of liver disease. In all cases with significant impairment of the metabolic capacity of the liver (e.g. acute viral hepatitis), dosage adjustments should be based on decreased (hepatic) clearance rather than on prolongation of halflife of the respective drug. In addition, oral doses of those drugs which under normal conditions are efficiently extracted from sinusoidal blood by hepatocytes should be further reduced in chronic liver disease (e.g. cirrhosis) as marked increases in their systemic bioavailability occur in the presence of altered hepatic blood flow.