The mechanisms of adverse drug effects have not been adequately classified. Here, we propose a comprehensive mechanistic classification of adverse drug effects that considers five elements: the Extrinsic chemical species (E) that initiates the effect; the Intrinsic chemical species (I) that it affects; the Distribution (D) of these species in the body; the (physiological or pathological) Outcome (O); and the Sequela (S), which is the adverse effect. This classification, which we have called EIDOS, describes the mechanism by which an adverse effect occurs; it complements the DoTS classification of adverse effects (based on clinical pharmacology), which takes into account Dose responsiveness, Time course, and Susceptibility factors. Together, these two classification systems, mechanistic and clinical, comprehensively delineate all the important aspects of adverse drug reactions; they should contribute to areas such as drug development and regulation, pharmacovigilance, monitoring therapy, and the prevention, diagnosis, and treatment of adverse drug effects.