Podophyllum hexandrum Royle, a rhizomatous perennial herb from the Berberidaceae family, is a highly reputed medicinal plant known for its lignan, podophyllotoxin. Podophyllotoxin and its semisynthetic derivativatives are potent anticancer agents. The semisynthetic analogues of podophyllotoxin are also used in the treatment of lung cancer, testicular cancer, neuroblastoma, hepatoma and other tumor diseases. While Podophyllotoxin acts as an inhibitor of the microtubule assembly, the cytotoxic action of its derevatives is based on the inhibition of topoisomerase. Owing to the ever-increasing demand of Podophyllum hexandrum for podophyllotoxin, it has been subjected to heavy collection from the wild. The anti-cancer lignan derivative podophyllotoxin is biosynthesized at very low quantities in intact Podophyllum hexandrum plant and the whole plant is harvested to isolate the bioactive lignan adding to the threats that the plant is currently facing. Therefore, biotechnological production of podophyllotoxin has been considered essential. The present review gives a brief introduction about the phytochemistry, pharmacology and biosynthesis of podophyllotoxin and also discusses the potential of biotechnology for production of podophyllotoxin to meet the increasing demand of this highly valued plant metabolite.