The phylogenetic position of several clitocyboid/pleurotoid/tricholomatoid genera previously considered incertae sedis is here resolved using an updated 6-gene dataset of Agaricales including newly sequenced lineages and more complete data from those already analyzed before. Results allowed to infer new phylogenetic relationships, and propose taxonomic novelties to accommodate them, including up to ten new families and a new suborder. Giacomia (for which a new species from China is here described) forms a monophyletic clade with Melanoleuca (Melanoleucaceae) nested inside suborder Pluteineae, together with the families Pluteaceae, Amanitaceae (including Leucocortinarius), Limnoperdaceae and Volvariellaceae. The recently described family Asproinocybaceae is shown to be a later synonym of Lyophyllaceae (which includes also Omphaliaster and Trichocybe) within suborder Tricholomatineae. The families Biannulariaceae, Callistosporiaceae, Clitocybaceae, Fayodiaceae, Macrocystidiaceae (which includes Pseudoclitopilus), Entolomataceae, Pseudoclitocybaceae (which includes Aspropaxillus), Omphalinaceae (Infundibulicybe and Omphalina) and the new families Paralepistaceae and Pseudoomphalinaceae belong also to Tricholomatineae. The delimitation of the suborder Pleurotineae (= Schizophyllineae) is discussed and revised, accepting five distinct families within it, viz. Pleurotaceae, Cyphellopsidaceae, Fistulinaceae, Resupinataceae and Schizophyllaceae. The recently proposed suborder Phyllotopsidineae (= Sarcomyxineae) is found to encompass the families Aphroditeolaceae, Pterulaceae, Phyllotopsidaceae, Radulomycetaceae, Sarcomyxaceae (which includes Tectella), and Stephanosporaceae, all of them unrelated to Pleurotaceae (suborder Pleurotineae) or Typhulaceae (suborder Typhulineae). The new family Xeromphalinaceae, encompassing the genera Xeromphalina and Heimiomyces, is proposed within Marasmiineae. The suborder Hygrophorineae is here reorganized into the families Hygrophoraceae, Cantharellulaceae, Cuphophyllaceae, Hygrocybaceae and Lichenomphaliaceae, to homogenize the taxonomic rank of the main clades inside all suborders of Agaricales. Finally, the genus Hygrophorocybe is shown to represent a distinct clade inside Cuphophyllaceae, and the new combination H. carolinensis is proposed. Taxonomic novelties: New suborder: Typhulineae Vizzini, Consiglio & P. Alvarado. New families: Aphroditeolaceae Vizzini, Consiglio & P. Alvarado, Melanoleucaceae Locq. ex Vizzini, Consiglio & P. Alvarado, Paralepistaceae Vizzini, Consiglio & P. Alvarado, Pseudoomphalinaceae Vizzini, Consiglio & P. Alvarado, Volvariellaceae Vizzini, Consiglio & P. Alvarado, Xeromphalinaceae Vizzini, Consiglio & P. Alvarado. New species: Giacomia sinensis J.Z. Xu. Stat. nov.: Cantharellulaceae (Lodge, Redhead, Norvell & Desjardin) Vizzini, Consiglio & P. Alvarado, Cuphophyllaceae (Z.M. He & Zhu L. Yang) Vizzini, Consiglio & P. Alvarado, Hygrocybaceae (Padamsee & Lodge) Vizzini, Consiglio & P. Alvarado, Lichenomphaliaceae (Lücking & Redhead) Vizzini, Consiglio & P. Alvarado. New combination: Hygrophorocybe carolinensis (H.E. Bigelow & Hesler) Vizzini, Consiglio & P. Alvarado. New synonyms: Sarcomyxineae Zhu L. Yang & G.S. Wang, Schizophyllineae Aime, Dentinger & Gaya, Asproinocybaceae T. Bau & G.F. Mou. Incertae sedis taxa placed at family level: Aphroditeola Redhead & Manfr. Binder, Giacomia Vizzini & Contu, Hygrophorocybe Vizzini & Contu, Leucocortinarius (J.E. Lange) Singer, Omphaliaster Lamoure, Pseudoclitopilus Vizzini & Contu, Resupinatus Nees ex Gray, Tectella Earle, Trichocybe Vizzini. New delimitations of taxa: Hygrophorineae Aime, Dentinger & Gaya, Phyllotopsidineae Zhu L. Yang & G.S. Wang, Pleurotineae Aime, Dentinger & Gaya, Pluteineae Aime, Dentinger & Gaya, Tricholomatineae Aime, Dentinger & Gaya. Resurrected taxa: Fayodiaceae Jülich, Resupinataceae Jülich. Citation: Vizzini A, Alvarado P, Consiglio G, Marchetti M, Xu J (2024). Family matters inside the order Agaricales: systematic reorganization and classification of incertae sedis clitocyboid, pleurotoid and tricholomatoid taxa based on an updated 6-gene phylogeny. Studies in Mycology 107: 67-148. doi: 10.3114/sim.2024.107.02.