Metabolizing enzymes and transporters play important roles in clearance and disposition of xenobiotics.Metabolizing enzymes mediated metabolism of xenobiotics results in activated or non-toxic metabolites.Transporters translocate xenobiotics across biological membrane to provide a mechanism of detoxification for any potentially harmful foreign substances in cells.Modulation of enzymes and transporters may reduce or enhance circulation or organ exposures of a substance by alteringits absorption, distribution, metabolism or excretion.In this presentation, the author use isocarbophos (ICP) and triptolide (TP) as two model substances to illustrate the roles of metabolizing enzymes and transporters in disposition and toxicity of xenobiotics (drug and toxicant).