CONTEXT: Liver disease is a serious ailment and the scenario is worsened by the lack of precise therapeutic regimens. Currently available therapies for liver ailments are not apposite and systemic toxicity inhibits their long term use. Medicinal plants have been traditionally used for treating liver diseases since centuries as the toxicity factor appears to be on the lower side. OBJECTIVE: Several phytochemials have been identified which have significant hepatoprotective activity with minimal systemic adverse effects which could limit their long term use. The scenario calls for extensive investigations which can lead to development of lead molecules for hepatoprotective molecules of future. This review deals with the biological activity, mode of action and toxicity and forthcoming application of some of these leads. METHODS: These generally have strong antioxidative potential and cause induction of antioxidant enzymes like superoxide dismutase, reduced glutathione and catalase. Additional mechanisms of hepatoprotection include stimulation of heme oxygenase-1 activity, inhibition of nitric oxide production, hepatocyte apoptosis and nuclear factor-κB activation. RESULTS AND CONCLUSION: Out of the several leads obtained from plant sources as potential hepatoprotective agents, silymarin, andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have been established as potent hepatoprotective agents. The hepatoprotective potential of several herbal medicines has been clinically evaluated. Significant efficacy has been seen with silymarin, glycyrrhizin and Liv-52 in treatment of hepatitis, alcoholic liver disease and liver cirrhosis.