A case of a 68-years-old female who was symptomatically treated with the codeine analog dextromethorphan because of a flu-like syndrome is herein reported. Five days later, she developed a cholestatic syndrome without fever or abdominal pain. Dextrometorphan was withdrawn and a rapid clinical improvement was observed, associated with decreasing levels of biochemical markers of cholestasis. Normal values were reached two months later. This type of adverse drug reaction, its potential pathogenic mechanisms and the therapeutic consequences are discussed.