Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, encompassing a disease spectrum ranging from non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH) as well as NASH-related fibrosis, cirrhosis and liver cancer. NASH presents unique liver pathology associated with disease progression which requires medication and/or intervention. There are currently no approved pharmacological therapies for NASH. The complicated pathogenesis of NASH involves intracellular and intercellular interaction in the liver as well as various molecular signaling pathways. NASH therapies represent huge unmet medical needs and drug market. This review provides a comprehensive update and summary of the current knowledge regarding hepatic nonparenchymal cells and their roles in NASH initiation and progression, with a discussion of novel therapeutic targets on specific hepatic cell types.