OBJECTIVE To present a framework within which population pharmacokinetic (PPK) studies should be designed and analyzed and discuss the application of developed PPK models. METHODS Information on PPK was retrieved from a MEDLINE search (1979–December 2003) of the literature and a bibliographic evaluation of review articles and books. This information is used in conjunction with experience to explain the design and analysis of PPK studies. Also, examples are included to demonstrate the usefulness of PPK. SYNTHESIS A great deal of thought must be given to the design and analysis of PPK studies (ie, development of PPK models). Models are of 2 primary types—descriptive and predictive—and the process applied to these models is necessarily different. An approach that ensures model applicability is presented. CONCLUSIONS PPK models have great utility, and the applications are many. They are very different from single-subject pharmacokinetic models and therefore require different approaches to model estimation.