This chapter is on approach to an unknown poisoning. Any substance if taken in any account, by any route and produces harmful effects over the body is called a poison. Poison may have local, systemic or combined effects. The effects of the poison depend on the route of administration, dose and concentration of the poison, physical and chemical state of the poison, area of application, age of the patient, idiosyncrasy and tolerance. Most of the poisonings are dose and concentration related. The diagnosis of the poisoning is dependent upon history, symptoms, signs and laboratory investigations. Every patient of unknown poisoning should be given 50% dextrose unless the finger stick shows euglycemia or hyperglycemia. Decontamination, enhanced elimination, antidotes are toxin played important role management of poisoning.