The crabs of the family Pinnotheridae are well known as commensals or parasites, mainly of molluscs and tubeworms. The phylogeny of the group, however, is poorly understood, with preliminary morphological and molecular studies questioning its monophyly. Here we used molecular genetic markers (16S, 12S mitochondrial; histone 3 nuclear) to infer a phylogeny for the family Pinnotheridae De Haan, 1833 to reevaluate the phylogeny and systematics at the level of its subfamilies and genera. Our molecular phylogeny indicated that Parapinnixa cortesi Thoma, Heard, & Vargas, 2005, Parapinnixa hendersoni Rathbun, 1918, Pinnotherelia laevigata H. Milne Edwards & Lucas, 1844, Sakaina yokoyai (Glassell, 1933), Tetrias fischerii (A. Milne-Edwards, 1867) and Tetrias scabripes Rathbun, 1898 should be removed from the family Pinnotheridae, while composition of the present subfamilies, Pinnotherinae De Haan, 1833 and Pinnothereliinae Alcock, 1900, must be revised. At generic level, Clypeasterophilus Campos, 1990, Dissodactylus Smith, 1870, Fabia Dana, 1851, Nepinnotheres Manning, 1993 and Pinnixa White, 1846 were not monophyletic in our analyses. With the exclusion of Pinnotherelia from Pinnotheridae, remaining species of Pinnothereliinae are assigned to Pinnixinae Števčić, 2005, a new subfamily based upon revision and elevation of rank for the tribe Pinnixini Števčić, 2005. In addition, we restructure membership of the subfamily Pinnotherinae and propose Pinnixulalinae, subfam. nov. to accommodate species that were excluded by molecular analyses from the other two subfamilies. These have a firm, wider-than-long carapace with clearly defined regions, strong legs that are usually tuberculate and very setose, and a third maxilliped with an elongate ischiomerus in which the ischium and merus may or may not be indistinguishably fused. Our analyses included 169 pinnotherid exemplars, representing almost half of the genera and about a quarter of the species presently recognised for the family. The relationships within and among some taxa are resolved to greater or lesser extent and the phylogenetic biodiversity of pinnotherid crabs is revealed. However, future publications will most likely result in a further increase in the number of taxa.