Drug-induced liver disease can result from dosage-dependent hepatotoxicity or from adverse reactions to drugs used in therapeutic dosage. The latter idiosyncratic hepatotoxins can cause clinical syndromes that mimic all known liver diseases, so that drugs must be considered as the possible causal agent for all unexplained cases of liver disease. The only specific antidote for dosage-dependent hepatotoxicity is n-acetylcysteine (and some other sulfhydryl donors), which is highly effective for the prevention of significant hepatotoxicity after acetaminophen overdose. Early diagnosis and prompt withdrawal of the offending drug is the key to successful management of most drug-induced liver diseases. The mainstay of treatment is supportive care, with careful monitoring for signs of acute liver failure or progression to chronic liver disease. In cases of liver failure, close liaison with a liver transplant center is crucial; referral for liver transplantation should be considered if standard transplant criteria are fulfilled. Pruritus is a major symptom of drug-induced cholestasis; protracted cases may respond to ursodeoxycholic acid. Corticosteroids can be considered for cases of drug-induced hepatitis, especially those with evidence of immune hypersensitivity, if no improvement is seen in 8 to 12 weeks. Although there are no controlled trials, some patients may respond favorably.