The Orthotrichaceae are found in all parts of the world including Antarctica. Crum (1987) considered the family to include 22 genera in five subfamilies. Most of the genera in the family are modest in size, but two are especially large: Orthotrichum (116 species, Lewinsky 1993) and Macromitrium (368 species, Crosby et al. 2000). The species figure for Macromitrium is undoubtedly high since it includes many untested species, mostly from South America, Africa, and the Malay Archipelago. At present, only about _ of the Macromitrium species have been reliably treated. In Central America there are eight genera distributed in three subfamilies: Orthotrichoideae (Orthotrichum), Macromitrioideae (Cardotiella, Ceuthotheca, Groutiella, Macrocoma, Macromitrium, Schlotheimia), and Zygodontoideae (Zygodon). Amphidium has often been treated in the Orthotrichaceae near Zygodon. Goffinet et al. (1998) and Stech (1999) on the basis of molecular evidence have shown that the genus has its affinities with the Haplolepideae.

The Orthotrichaceae occur on trees or rocks and exhibit a tremendous amount of  character variation that makes the family difficult to define. They are mostly small to modest-sized, with plants either erect and occurring in tufts or prostrate, often with a mat‑like growth form. Members of the Orthotrichaceae have leaves with strong, single costae, mostly lack strong alar cell differentiation, and often have thickened leaf cell walls. The Orthotrichaceae are so gametophytically variable that nearly all other moss leaf character states can be found in at least some members of the family.

The Orthotrichaceae have a reduced and highly modified diplolepidous peristome in which the cellular pattern on the both the exostome and/or endostome can be so disorganized it is difficult to interpret. As a rule the Orthotrichaceae exostome teeth are more thickened on the outside than the inside and the endostome has a short basal membrane, stout segments alternating with the exostome teeth, and no cilia. Opposite endostomial segments have been reported in some species of  Schlotheimia (Vitt 1981a). Although these segments are indeed physically opposite the exostome teeth, the peristomial pattern in these species is the same as that found in species with alternating segments. Orthotrichaceous peristomes with opposite segments thus represent a minor peristome variation (see Shaw & Rohrer 1984, Shaw 1986). In general the Orthotrichaceae have a  4:2:4 or 4:2:2 peristomial pattern which occasionally is modified into a 4:2:3 pattern. The presence of a modified 4:2:3 peristomial pattern in some members of the Orthotrichaceae along with the stoutness of its endostomial segments has lead to speculation that its peristome is derived within the Diplolepideae (Shaw 1986) and may have given rise to the haplolepidous peristome (Lewinsky 1989). Shaw (1986) has shown that the peristomial pattern for Drummondia is either 2:3 or 2:6 and on this evidence as well as molecular evidence utilizing the rbcL gene (Goffinet et al.1998) the genus has been transferred to the Grimmiales (Buck & Goffinet 2000).