An important issue in toxicology is the suitability of the data obtained with experimental animals for human risk assessment. Because it is not possible to use humans in long-term toxicological studies, the use of animals will continue. However, the data obtained in animal studies can be better extrapolated to the patient by utilizing bridging studies with in vitro models of human drug metabolism. There are 2 basic categories of in vitro methods for the examination of human liver drug metabolism. The first group of in vitro methods consists of the cellular models, which include primary hepatocytes, liver slices, and cell lines. The second group is the use of preparations of the drug-metabolizing enzymes such as tissue homogenates, subcellular fractions, and isolated enzymes. Studies modeling both the human and experimental animal metabolism of a drug are useful in the design of toxicological studies. In vitro studies can identify metabolites, species-specific metabolic routes, and the experimental animal model that best reflects the potential human exposure to the drug and its metabolites. This information can also be useful in the design of the clinical studies by identifying human metabolites, the enzymes responsible for the metabolic clearance of the drug, the effects of genetics and other host factors on the metabolism of the drug, and potential drug-drug interactions. An example of how such information is generated and interpreted is presented.