The histologic assessment of acute and chronic liver disease is based on an accurate description of the pattern of injury within the tissue specimen. Interpretation of the injury pattern requires review of the associated clinical and laboratory features. The morphologic interpretation achieves relevance only if it satisfactorily explains the clinical syndrome. Clinical characterization of the liver disease as having a hepatitic or cholestatic nature is useful in focusing the histologic assessment. The principal histologic patterns have hepatitic, steatotic, biliary, granulomatous, vascular, and metabolic designations, and mixed clinical and histologic patterns are possible. The goal of this review is to optimize the yield from the liver biopsy examination by indicating the importance of a systematic analysis of the tissue specimen and the crucial need for correlating the clinical and histologic patterns of liver injury. Meaningful histologic interpretations reflect the collaborative effort of the pathologist and the clinical physician. Neoplastic changes typically are cytologic transformations rather than injury patterns, and they are not discussed here.