Drug induced hepatotoxicity has been reported infrequently with sulfonylureas. For glimepiride, a second-generation sulfonylurea there is no report of hepatotoxicity in English literature. A patient with non-insulin-dependent diabetes mellitus who developed cholestatic liver injury soon after initiation of glimepiride therapy is presented. Complete work-up disclosed no other cause for hepatotoxicity including negative serological results for viral hepatitis. Liver biopsy was consistent with drug-induced cholestasis. The patient recovered 50 days after stopping glimepiride with no further recurrences.