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Elicitation by chemical means including heavy metals is one of a novel technique for drug discoveries. In this review, the effect of heavy metals on animal, plants and microorganisms for the production of novel compounds with the unique structures has been discussed. The number of parameters such as metal concentration, type, dose, treatment schedule, duration of metal exposure, and nutrient composition are significant factors altering the secondary metabolites production. The detailed illustrated diagram representing the mode of action of metal stress has also been discussed. This is the first article reporting all the novel compounds produced from plants and microorganisms in response to metal-stress with their pharmacological potential. This new technique opens the new way for drug discovery from natural products.