In the light of a phylogenetic reconstruction based on a multi-loci data set including sequence data from all three compartments (plastome: (rps4)–trnF, rpl16 group II intron; chondrome: nad5 group I intron; nuclear: ITS1&2) the Orthostichellaceae are described as a new family of pleurocarpous mosses. It is distributed mainly in the Neotropics and tropical Africa, and provisionally contains the genera Dixonia (Asia, 1 species), Afrothamnium gen. nov. (Africa and Neotropics, 1 sp.), Pinnatidendron gen. nov. (Africa and Neotropics, 1 sp.), Deslooveria gen. nov. (Africa and French Guiana, 5 spp.), Scabrellifolium gen. nov. (Neotropics and Africa, 2 spp.), and Orthostichella (Neotropics and Africa, 9 spp.). In the Neckeraceae we describe Dannorrisia gen. nov. (N. America, 1 sp.), Austrothamnium gen. nov. (Australasia, 2 spp.), and Bryobuckia gen. nov. (endemic to Chile, 7 spp.). Porotrichum s.str. becomes an essentially Neotropical genus and it contains the formerly recognized genera Porotrichopsis and Porotrichodendron. Thamnobryum s.str. is distributed exclusively in the Northern Hemisphere and is largely temperate. The mainly Macaronesian Echinodiaceae becomes a family of two genera, Echinodium (3 spp.) and Pseudomalia gen. nov. (1 sp.). The morphological evolution in the Orthostichellaceae is discussed based on the phylogeny.