Drugs can induce almost all forms of acute and chronic liver disease, with some drugs more than one type of hepatic reaction. Many drugs cause elevate liver enzymes with apparently no clinically significant adverse effect. Drug induced liver injury is a diagnosis of exclusion that rests upon ruling out other common causes of liver disease. Hepatotoxicity has been reported with agents such as anti-tubercular drugs, NSAIDs, hypolipidimics, antiepileptic drugs etc., there are few evidences of hepatotoxicity with Phenobarbital on prolonged use. We here report a case of hepatotoxicity induced by prolonged use of Phenobarbital in a 30 year old female patient of enteric fever, having increased liver enzymes.