Allopurinol is frequently used for the treatment of hyperuricemia and gout. Sometimes, a life-threatening reaction develops, as is illustrated by the following case report. We describe a 60-year-old male patient who was treated with allopurinol because of asymptomatic hyperuricemia, and he was presented with fever, skin rash, eosinophilia, worsening renal function and vanishing bile duct syndrome. In this report, we discussed vanishing bile duct syndrome as a serious side effect of allopurinol, and we briefly reviewed the etiology, prevention, and treatment modalities for vanishing bile duct syndrome.