Pharmacodynamic modeling is based on a quantitative integration of pharmacokinetics, pharmacological systems, and (patho-) physiological processes for understanding the intensity and time-course of drug effects on the body. Application of such models to the analysis of meaningful experimental data allows for the quantification and prediction of drug-system interactions for both therapeutic and adverse drug responses. In this chapter, commonly used mechanistic pharmacodynamic models are presented with respect to their important features, operable equations, and signature profiles. In addition, literature examples showcasing the utility of these models to adverse drug events are highlighted. Common model types that are covered include simple direct effects, biophase distribution, indirect effects, signal transduction, and irreversible effects.