Together with drug metabolising enzymes, transmembrane transporters are important determinants of drug metabolism and drug clearance by the liver. Hepatic uptake of organic anions, cations, prostaglandins and bile salts is supported by dedicated transporter proteins in the basolateral (sinusoidal) membrane of hepatocytes: OATPs, OATs, OCTs, PGTs and NTCP, respectively. ATP-binding cassette (ABC) transporter proteins in the canalicular membrane of hepatocytes mediate the hepatic efflux of drugs, bile salts and metabolites against a steep concentration gradient from liver to bile. This transport is driven by ATP hydrolysis. Drugs, endogenous metabolites, bile salts and cytokines affect the expression levels of these transporters. They act through a family of ligand-activated transcription factors, the nuclear hormone receptors. Consequently, the levels of the various transporter proteins are subject to genetic polymorphism in the encoding genes as well as in these transcription factors. Adverse drug reactions may be caused by genetic or disease-induced variations of transporter expression or drug-drug interactions at the level of these transporters.