Drugs and their metabolites are eliminated mainly by excretion into urine and bile. Studies in whole animals, isolated organs, cells, and membrane vesicles led to the conclusion that different transport systems are responsible for the transport of different classes of organic compounds (small, large, anionic, and cationic). In the early 1990s, functional expression cloning resulted in the identification of the first transporters for organic anions and cations. Eventually, all the major transport systems involved in the uptake of these organic compounds were cloned and characterized, and we now know that they belong to the organic anion transporters (OATs) and organic cation transporters (OCTs) of the SLC22A superfamily and the organic anion-transporting polypeptides (OATPs) of the SLCO superfamily of polyspecific drug transporters. Today we can explain, at the molecular level, why small and hydrophilic organic compounds are excreted predominantly through urine whereas large and amphipathic compounds are excreted mainly through bile, and we can start to predict drug-drug interactions in the case of new compounds.