Podophyllotoxin is a non-alkaloid toxin lignan isolated from the roots and rhizomes of *Podophyllum* species, such as *Podophyllum peltatum* (American mayapple) and *Podophyllum hexandrum* (Himalayan mayapple). It is a potent cytotoxic agent with a complex fused tetracyclic structure featuring a lactone ring. Its primary and most significant application is in medicine as a precursor for the semi-synthesis of important anticancer drugs, notably etoposide, teniposide, and etopophos. These drugs are topoisomerase II inhibitors used in the treatment of various cancers, including testicular cancer, small cell lung cancer, and lymphomas. Podophyllotoxin itself is also directly used as the active pharmaceutical ingredient (API) in topical solutions for the treatment of genital warts caused by human papillomavirus (HPV), where it acts as a potent antimitotic agent by binding to tubulin and inhibiting microtubule assembly. Due to its natural origin and specific, potent biological activity, it is classified as a plant-derived natural product with direct pharmaceutical utility. Its supply relies heavily on extraction from plant sources, although synthetic routes are an area of research. Handling requires caution due to its high toxicity and potential for severe side effects if administered systemically.