Abstract: Systems toxicology is a new branch of science that aims to decode the mechanisms by which external stimuli cause toxic effects from the perspective of body systems. It usually requires integration of information from multiple biological levels to cope with modelling and prediction purposes. In this review, two primary research areas of systems toxicology, toxicokinetics and toxicodynamics, are introduced, and the history and recent progress of the latter are discussed. The Toxicity Testing in the 21st Century: A Vision and a Strategy report called for focus on perturbations of key toxicity pathways to base the future testing platform. Another two pathwaybased approaches, mode of action (MOA) and adverse outcome pathway (AOP), are also main efforts in toxicodynamics and provide a framework for hazard identification, toxicity testing, and human health risk assessment. Attempts in developing AOPs are in the initial stage, and open questions encourage future progress in this field.