The applications of pharmacokinetic modeling to the prediction of tissue residues of drugs in food‐producing animals are reviewed. The properties of the one‐compartment open model are discussed, and the application of this model to the serum levels, urine outputs, and tissue residues of sulfamethazine and its metabolites in sheep is described. The properties of the two‐compartment model are discussed, and the application of this model to the serum levels and urine outputs of dicloxacillin in humans is described. Complexities encountered with drugs such as pentobarbital, the tetracyclines, etidronate, and salicylate are discussed as examples of pharmacokinetic behavior that make both modeling and tissue residue prediction difficult.