Acetaminophen is a widely used analgesic agent, but at the same time, overdosing with acetaminophen is one of the leading causes of hospital admission. The administration of the specific antidote, N-acetylcysteine, should be initiated but renal replacement therapy, therapeutic plasmapheresis or even liver transplantation may be necessary. We present a case of severe metabolic lactic acidosis and coma after massive intake of acetaminophen. The patient was treated with N¬-acetylcysteine at a higher dose and received hemodialysis. He presented with severe liver failure, and despite optimal treatment, except liver transplantation, he died 70 hours after hospitalization. We describe the treatment of massive acetaminophen overdose and discuss the literature about the need for higher doses of N-acetylcysteine in these situations and the need for increasing doses, when co-administering hemodialysis. Other treatment strategies are mentioned.