Podophyllotoxin, a lignan derivative, is a chemotherapeutic agent and acts as a precursor molecule for crucial anti-cancer drugs such as teniposide, etopophos and etoposide. Major source of this secondary metabolite is Podophyllum hexandrum Royle, an endangered medicinal plant of the Himalayan region. Although its chemical synthesis is possible, it is not economically feasible, hence industrial demands of podophyllotoxin are met from the rhizomes of wild P. hexandrum Royle (Himalayan mayapple) and P. peltatum L. (American mayapple). Overcollection of rhizomes to meet the demand has resulted in drastic reduction of Podophyllum L. population in the wild, and the market demand is much more than the annual supply. Elicitation is an effective method for enhancing secondary metabolite production. This chapter highlights the recent progress vis-a-vis the use of elicitors for the production of podophyllotoxin.