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This paper describes how we are applying physiologically based models of pharmacokinetics as an integrated part in the research and preclinical development of novel drugs. The modeling and simulation tools and techniques used are briefly reviewed and the strategy for application in drug research is described. Three examples illustrate how such models may be applied at different stages ranging from early application prior to in vivo studies, through clinical candidate selection to the estimation of human kinetics and dose selection prior to clinical studies. Although there are obvious restrictions related to limited input data at the earlier stages, the examples illustrate some of the advantages of the approach compared to other more empirical methods. These advantages will be fully exploited with more widespread use of physiological models as powerful and user-friendly software make them accessible to non-specialists.