Fish liver microscopic structure is an integrator of physiological and biochemical function which, when altered, may produce biomarkers of prior exposure to toxicants. The liver has a key role in xenobiotic metabolism and excretion, digestion and storage, and production of yolk protein. Thus, alterations in structure are expected under certain toxic conditions. A series of lesions associated with chronic liver toxicity are described, illustrated, and evaluated for their potential usefulness as biomarkers of toxicant exposure. Where possible, the potentially confounding morphological changes associated with infectious disease, season, sex, and nutritional state are differentiated from toxicant-induced lesions. Hepatocyte coagulative necrosis, hepatocyte regenerative foci, spongiosis hepatis, and neoplasia appear to be the most promising liver structural biomarkers of prior exposure to toxicants.