Positron emission tomography (PET) is increasingly being used in anticancer drug development. The technique is applicable to studies of drug delivery, and where specific probes are available, to provide pharmacodynamic readouts noninvasively in patients. Mathematical modeling of the imaging data enhances the quality of information that is obtained from such studies. This section provides a review of the PET methodologies that have been used for the development of new cancer therapies. Other than imaging of radiolabeled drugs, PET modeling has found extensive application in studies with 2-[11C]thymidine, [18F]fluorodeoxyglucose, H2(15)O, C15O, and receptor ligands.