Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western hemisphere and is growing as an indication for liver transplantation. There are currently no approved therapies for NAFLD, especially its aggressive phenotype non-alcoholic steatohepatitis (NASH). However, there has been an explosion of information related to NASH that provides detailed data on the molecular pathogenesis of NASH and its progression to cirrhosis. The current review summarizes the pathophysiological rationale for the selection of specific targets for the treatment of NASH and provides an overview of the current strategies being used for the treatment of NASH and the pathophysiological rationale for the use of these strategies. Specifically, those targets that are being studied in both alcoholic and non-alcoholic steatohepatitis are also mentioned.