Poisoning by cytotoxic mushrooms (Amanita phalloides and related species) is associated with severe morbidity and a high mortality rate. Due to the difficulty of performing controlled studies and to the poor knowledge of the pharmacodynamics of toxins in human poisoning, there is considerable debate about appropriate treatment, particularly the feasibility and the efficacy of detoxification. Because circulating amatoxins can be detected in the serum of poisoned patients as long as 30 h after ingestion, a detoxification treatment should ideally increase the rate of toxin elimination in order to minimize the toxic exposure of highly susceptible cells, such as hepatocytes. We found forced diuresis to be the most effective procedure for toxin removal. Other techniques, such as plasmapheresis and peritoneal dialysis, proved much less useful for this purpose. The administration of cathartics, adsorbent agents, and gastroduodenal lavage, are indicated for preventing further absorption of toxins from the gut. An important part of therapy is early and vigorous volume replacement, to correct the severe hypovolemia which results from massive fluid loss during the cholera-like phase of intoxication. Use of this therapeutic approach in 53 patients with amatoxin poisoning resulted in a high survival rate and a low incidence of severe liver injury.