A six-gene phylogeny of the Inocybaceae is presented to address classification of major clades within the family. Seven genera are recognized that establish a global overview of phylogenetic relationships in the Inocybaceae. Two genera—Nothocybe and Pseudosperma—are described as new. Two subgenera of Inocybe—subg. Inosperma and subg. Mallocybe—are elevated to generic rank. These four new genera, together with the previously described Auritella, Tubariomyces, and now Inocybe sensu stricto, constitute the Inocybaceae, an ectomycorrhizal lineage of Agaricales that associates with at least 23 plant families worldwide. Pseudosperma, Nothocybe, and Inocybe are recovered as a strongly supported inclusive clade within the family. The genus Nothocybe, represented by a single species from tropical India, is strongly supported as the sister lineage to Inocybe, a hyperdiverse genus containing hundreds of species and global distribution. Two additional inclusive clades, including Inosperma, Tubariomyces, Auritella, and Mallocybe, and a nested grouping of Auritella, Mallocybe, and Tubariomyces, are recovered but with marginal statistical support. Overall, the six-gene data set provides a more robust phylogenetic estimate of relationships within the family than do single-gene and single-gene-region estimates. In addition, Africa, India, and Australia are characterized by the most genera in the family, with South America containing the fewest number of genera. A total of 180 names are recombined or proposed as new in Inosperma, Mallocybe, and Pseudosperma. A key to genera of Inocybaceae is provided