Phylogenetic relationships within Hesionidae Grube, 1850 are assessed via maximum parsimony and maximum likelihood analyses of mitochondrial (cytochrome c oxidase subunit I and 16S rRNA) and nuclear (18S rRNA, and 28S rRNA) data. The analyses are based on 42 hesionid species; six of these being new species that are described here. The new species, all from deep (>200 m depth) benthic environments (including whale falls) in the eastern Pacific, are Gyptis shannonae, sp. nov., Neogyptis julii, sp. nov., Sirsoe sirikos, sp. nov., Vrijenhoekia ketea, sp. nov., Vrijenhoekia falenothiras, sp. nov., and Vrijenhoekia ahabi, sp. nov. The molecular divergence among the new members of Vrijenhoekia is pronounced enough to consider them cryptic species, even though we cannot distinguish among them morphologically. Our results also showed that the subfamily Hesioninae Grube, 1850, as traditionally delineated, was paraphyletic. We thus restrict Hesioninae to include only Hesionini Grube, 1850 and refer the remaining members to Psamathinae Pleijel, 1998. The present study increases the number of hesionid species associated with whale falls from one to six and markedly increases the number of described deep-sea hesionid taxa. There appear to have been multiple colonisations of the deep sea from shallow waters by hesionids, though further sampling is warranted.