The fungal kingdom poses major catastrophic threats to humanity but these are often unappreciated and minimized, in biological threat assessments. The causes for this blind spot are complex and include the remarkable natural resistance of humans to pathogenic fungi, the lack of contagiousness of human fungal diseases, and the indirectness of fungal threats, which are more likely to mediate their destructive effects on crops and ecosystems. A review of historical events reveals that the fungal kingdom includes major threats to humanity through their effects on human health, agriculture, and destruction of materiel. A major concern going forward is the likelihood that physiological adaptations by fungal species to global warming will bring new fungal threats. Fungal threats pose significant challenges specific to this group of organisms including the potential for intercontinental spread by air currents, capacity for rapid evolution, a paucity of effective drugs, the absence of vaccines, and increasing drug resistance. Preparedness against bio-catastrophic risks must include consideration of the threats posed by fungi, which in turn requires a greater investment in mycology-related research.