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To assess the evolving global epidemiology of mushroom poisoning and to identify new and emerging mushroom poisonings and their treatments, a descriptive analysis and review of the world’s salient scientific literature on mushroom poisoning was conducted.Data sources from observation studies conducted over the period 1959–2002, and describing 28,018 mushroom poisonings since 1951, were collected from case reports, case series, regional descriptive studies, meta-analyses, and laboratory studies of mushroom poisonings and the toxicokinetics of mycotoxins.Studies included in the review were selected by a MEDLINE search, 1966–2004, an Ovid OLDMEDLINE search, 1951–1965, and a medical library search for sources published before 1951.To better guide clinicians in establishing diagnoses and implementing therapies, despite confusing ingestion histories, data were extracted to permit an expanded syndromic classification of mushroom poisoning based on presentation timing and target organ systemic toxicity.The final 14 major syndromes of mushroom poisoning were stratified first by presentation timing and then by target organ systemic toxicity and included early (<6 hrs), late (6–24 hrs), and delayed syndromes (≥1 day). There were eight early syndromes (four neurotoxic, two gastrointestinal, two allergic); three late syndromes (hepatotoxic, accelerated nephrotoxic, erythromelalgia); and three delayed syndromes (delayed nephrotoxic, delayed neurotoxic, rhabdomyolysis). Four new mushroom poisoning syndromes were classified including accelerated nephrotoxicity (Amanita proxima, Amanita smithiana), rhabdomyolysis (Tricholoma equestre, Russula subnigricans), erythromelalgia (Clitocybe amoenolens, Clitocybe acromelalgia), and delayed neurotoxicity (Hapalopilus rutilans). In addition, data sources were stratified by three chronological time periods with >1,000 confirmed mushroom ingestions reported and tested for any statistically significant secular trends in case fatalities from mushroom ingestions over the entire study period, 1951–2002.Since the 1950s, reports of severe and fatal mushroom poisonings have increased worldwide. Clinicians must consider mushroom poisoning in the evaluation of all patients who may be intoxicated by natural substances. Since information on natural exposures is often insufficient and incorrect, a new syndromic classification of mushroom poisoning is recommended to guide clinicians in making earlier diagnoses, especially in cases where only advanced critical care, including organ transplantation, may be life saving.