The ascomycete family Nectriaceae (Hypocreales) includes numerous important plant and human pathogens, as well as several species used extensively in industrial and commercial applications as biodegraders and biocontrol agents. Members of the family are unified by phenotypic characters such as uniloculate ascomata that are yellow, orange-red to purple, and with phialidic asexual morphs. The generic concepts in Nectriaceae are poorly defined, since DNA sequence data have not been available for many of these genera. To address this issue we performed a multi-gene phylogenetic analysis using partial sequences for the 28S large subunit (LSU) nrDNA, the internal transcribed spacer region and intervening 5.8S nrRNA gene (ITS), the large subunit of the ATP citrate lyase (acl1), the RNA polymerase II largest subunit (rpb1), RNA polymerase II second largest subunit (rpb2), [alpha]-actin (act), [beta]-tubulin (tub2), calmodulin (cmdA), histone H3 (his3), and translation elongation factor 1-alpha (tef1) gene regions for available type and authentic strains representing known genera in Nectriaceae, including several genera for which no sequence data were previously available. Supported by morphological observations, the data resolved 47 genera in the Nectriaceae. We re-evaluated the status of several genera, which resulted in the introduction of six new genera to accommodate species that were initially classified based solely on morphological characters. Several generic names are proposed for synonymy based on the abolishment of dual nomenclature. Additionally, a new family is introduced for two genera that were previously accommodated in the Nectriaceae. Key words: Generic concepts, Nectriaceae, Phylogeny, Taxonomy. Taxonomic novelties: New family: Tilachlidiaceae L. Lombard & Crous; New genera: Aquanectria L. Lombard & Crous, Bisifusarium L. Lombard, Crous & W. Gams, Coccinonectria L. Lombard & Crous, Paracremonium L. Lombard & Crous, Rectifusarium L. Lombard, Crous & W. Gams, Xenoacremonium L. Lombard & Crous; New species: Mariannaea humicola L. Lombard & Crous, Neocosmospora rubicola L. Lombard & Crous, Paracremonium inflatum L. Lombard & Crous, P. contagium L. Lombard & Crous, Pseudonectria foliicola L. Lombard & Crous, Rectifusarium robinianum L. Lombard & Crous, Xenoacremonium falcatus L. Lombard & Crous, Xenogliocladiopsis cypellocarpa L. Lombard & Crous; New combinations: Aquanectria penicillioides (Ingold) L. Lombard & Crous, A. submerse (H.J. Huds.) L. Lombard & Crous, Bisifusarium biseptatum (Schroers, Summerbell & O'Donnell) L. Lombard & Crous, B. delphinoides (Schroers, Summerbell, O'Donnell & Lampr.) L. Lombard & Crous, B. dimerum (Penz.) L. Lombard & Crous, B. domesticum (Fr.) L. Lombard & Crous, B. lunatum (Ellis & Everh.) L. Lombard & Crous, B. nectrioides (Wollenw.) L. Lombard & Crous, B. penzigii (Schroers, Summerbell & O'Donnell) L. Lombard & Crous, Calonectria candelabra (Vi egas) Rossman, L. Lombard & Crous, C. cylindrospora (Ellis & Everh.) Rossman, L. Lombard & Crous, Clonostachys apocyni (Peck) Rossman, L. Lombard & Crous, C. aurantia (Penz. & Sacc.) Rossman, L. Lombard & Crous, C. blumenaviae (Rehm) Rossman, L. Lombard & Crous, C. gibberosa (Schroers) Rossman, L. Lombard & Crous, C. manihotis (Rick) Rossman, L. Lombard & Crous, C. parva (Schroers) Rossman, L. Lombard & Crous, C. tonduzii (Speg.) Rossman, L. Lombard & Crous, C. tornata (Hohn.) Rossman, L. Lombard & Crous, Coccinonectria pachysandricola (B.O. Dodge) L. Lombard & Crous, C. rusci (Lechat, Gardiennet & J. Fourn.) L. Lombard & Crous, Hydropisphaera fusigera (Berk. & Broome) Rossman, L. Lombard & Crous, Ilyonectria destructans (Zinssm.) Rossman, L. Lombard & Crous, I. macroconidialis (Brayford & Samuels) Rossman, L. Lombard & Crous, Mariannaea catenulatae (Samuels) L. Lombard & Crous, Nectriopsis rexiana (Sacc.) Rossman, L. Lombard & Crous, Neocosmospora ambrosia (Gadd & Loos) L. Lombard & Crous, N. falciformis (Carri on) L. Lombard & Crous, N. illudens (Berk.) L. Lombard & Crous, N. ipomoeae (Halst.) L. Lombard & Crous, N. monilifera (Berk. & Broome) L. Lombard & Crous, N. phaseoli (Burkh.) L. Lombard & Crous, N. plagianthi (Dingley) L. Lombard & Crous, N. ramosa (Bat. & H. Maia) L. Lombard & Crous, N. solani (Mart.) L. Lombard & Crous, N. termitum (Hohn.) L. Lombard & Crous, N. tucumaniae (T. Aoki, O'Donnell, Yos. Homma & Lattanzi) L. Lombard & Crous, N. virguliformis (O'Donnell & T. Aoki) L. Lombard & Crous, Neonectria candida (Ehrenb.) Rossman, L. Lombard & Crous, Penicillifer diparietisporus (J.H. Miller, Giddens & A.A. Foster) Rossman, L. Lombard & Crous, Rectifusarium ventricosum (Appel & Wollenw.) L. Lombard & Crous, Sarcopodium flavolanatum (Berk. & Broome) L. Lombard & Crous, S. mammiforme (Chard on) L. Lombard & Crous, S. oblongisporum (Y. Nong & W.Y. Zhuang) L. Lombard & Crous, S. raripilum (Penz. & Sacc.) L. Lombard & Crous, Sphaerostilbella penicillioides (Corda) Rossman, L. Lombard & Crous, S. aurifila (W.R. Gerard) Rossman, L. Lombard & Crous, Volutella asiana (J. Luo, X.M. Zhang & W.Y. Zhuang) L. Lombard & Crous, Xenoacremonium recifei (Leao & Lobo) L. Lombard & Crous; New name: Mariannaea pinicola L. Lombard & Crous; Typification: Epitypification (basionyms): Rectifusarium ventricosum Appel & Wollenw., Xenogliocladiopsis eucalyptorum Crous & W.B. Kendr..