Pathologists have long been involved in clinical diagnosis and investigative studies of various forms of liver disease, including alcoholic liver disease. The concept that progressive fatty liver disease may result from causes other than alcohol toxicity can be noted in the literature. However, acceptance of this as a bona fide form of liver disease has been credited to an in-depth study published in 1980 of patients gathered from cases in the files of the pathology department of the Mayo Clinic in whom liver biopsies showed histological similarities to alcoholic steatohepatitis, but for whom clinical evidence of alcohol use was absent. Subsequent studies of the natural history and pathogenesis of non-alcoholic steatohepatitis have relied on detailed histopathological correlations. This chapter will elucidate the constellation of microscopic findings, the issues of concern for pathological evaluation and the knowledge to date of their significance in various forms of fatty liver disease.