Trichothecenes are a group of well-known mycotoxins which are produced by the various fungal species involved in the Hypocreales order. Fusarium, Myrothecium, Spicellum, Stachybotrys, Cephalosporium, Trichoderma, and Trichothecium are the major genus in which the trichothecene biosynthetic pathway presents in their metabolism. In Fusarium spp., the Tri5 gene cluster is responsible for trichothecene biosynthesis. However, different tri gene orthologues are identified and characterized for trichothecene production in other species. Trichothecene mycotoxins are subclassed to type -A, -B, -C, and -D in terms of their structural differences in Fusarium species. The toxicity of trichothecenes, their cellular effects, the pathogenesis caused by their accumulation, and the clinical aspect of direct Fusarium infection become widespread topics because both organisms themselves and their associated mycotoxins can affect the host with a systemic potential. Because of their toxicity levels for both animals and humans, investigations of these mycotoxins’ biosynthetic pathways and regulations, conducting sub-classification, and distribution, revealing their toxicity mechanisms on different organisms and maintaining various potential quelling researches have genuine prominence on both agricultural and clinical perspective.