From the year 2000 onwards, physiologically based pharmacokinetic (PBPK) models in the field of drug research and development have been increasingly used. This proliferation of applications was prompted by the availability of new data and computational approaches required for the parameterization of PBPK models, as well as the availability of commercial software platforms. PBPK approaches have been used to predict drug pharmacokinetics in humans based on nonclinical data, the potential for drug-drug interactions and the expected changes in the pharmacokinetics in case of different physiopathological conditions. In this respect, PBPK is also assuming a more important role in regulatory submissions. Although PBPK methodologies are not perfect yet, their continuous and consistent application is providing a more profound understanding of the determinants of the drug absorption and disposition of new and candidate drugs. We are confident that, with increased use, PBPK methodologies will gradually improve in their predictive capabilities.