Non-alcoholic steatohepatitis morbidity and mortality is on the rise due to the obesity pandemic. Its pathophysiology is not well understood and implies complex interactions between local hepatic cells populations, adipocytes, immune effectors that lead to hepatic lipid excess, lipotoxicity, cellular stress and inflammation, as well as programmed cell death. A better understanding of these pathogenic interactions would allow better identification of therapeutic targets in a disease that has no known pharmacological therapy until now.