Occupational and environmental exposures to industrial chemicals are well known to cause hepatotoxicity and liver injury.However,despite extensive evidence showing that exposure can lead to disease,current research approaches and regulatory policies fail to address the possibility that subtle changes caused by low level exposure to chemicals may also enhance preexisting conditions.In recent years,the conceptual understanding of the contribution of environmental chemicals to liver disease has progressed significantly.Mitochondria are often target of toxicity of environmental toxicants resulting in multisystem disorders involving different cells,tissues,and organs.Here,we review persistent mal-adaptive changes to mitochondria in response to environmental toxicant exposure as a mechanism of hep-atotoxicity.With better understanding of the mechanism(s)and risk factors that mediate the initiation and progression of toxicant-induced liver disease,rational targeted therapy can be developed to better predict risk,as well as to treat or prevent this disease.