Liver, the most important metabolic organ of the body, is also the major organ for the detoxification of the blood stream. If the accumulation of toxins is faster than their removal by liver, hepatic damage occurs. Although synthetic drugs are available in the market, long-term use of such drugs has consequential side effects. Therefore, the growing need to find safe, cost-effective drugs devoid of adverse effects is spawning extensive research. Mushrooms are rising as a major medicinal food and pharmaceuticals. This review summarizes the medicinal value of different edible mushrooms on free radical–, xenobiotic-, and drug-induced hepatotoxicity. © 2016 Taylor & Francis.