A major part of the science of pharmacokinetics is the modeling of the underlying processes that contribute to drug disposition. The purpose of pharmacokinetic models is to summarize the knowledge gained in preclinical and clinical studies at various stages in drug development and to rationally guide future studies with the use of adequately predictive models. This review highlights a variety of recent advances in mechanistic pharmacokinetic modeling. It is aimed at a broad audience, and hence, an attempt was made to maintain a balance between technical information and practical applications of pharmacokinetic modeling. It is hoped that drug researchers from all disciplines would be able to get a flavor of the function and capacity of pharmacokinetic modelers and their contribution to drug development. While this review is not intended to be a technical reference on modeling approaches, the roles of statistical applications and population methodologies are discussed where appropriate.