Allopurinol hypersensitivity syndrome (AHS) is a severe reaction which is potentially lethal. Exanthematous rash, fever, eosinophilia, and other severe reactions such as toxic epidermal necrolysis, acute vasculitis, and severe hepatic and renal dysfunctions are manifestations of this syndrome. The authors report a case of lethal massive hepatic necrosis due to allopurinol in a patient with the asymptomatic hyperuricemia. They also describe the risk factors most frequently associated with the development of AHS and the strategy for its prevention and consequent reduction of the mortality associated with this syndrome.