The millipede family Xystodesmidae includes 486 species distributed primarily in temperate deciduous forests in North America and East Asia. Species diversity of the family is greatest in the Appalachian Mountains of the eastern United States, with 188 species. Although the group includes notable taxa such as those that are bioluminescent and others that display Müllerian mimicry, producing up to 600 mg of cyanide, basic alpha-taxonomy of the group is woefully incomplete and more than 50 species remain undescribed in the Appalachian Mountains alone. In order to establish a robust phylogenetic foundation for addressing compelling evolutionary questions and describing species diversity, we assembled the largest species phylogeny (in terms of species sampling) to date in the Diplopoda. We sampled 49 genera (out of 57) and 247 of the species in the family Xystodesmidae, recollecting fresh material from historical type localities and discovering new species in unexplored regions. Here, we present a phylogeny of the family using six genes (four mitochondrial and two nuclear) and include pivotal taxa omitted from previous studies including Nannaria, Erdelyia, taxa from East Asia, and 10 new species. We show that 6 of the 11 tribes are monophyletic, and that the family is paraphyletic with respect to the Euryuridae and Eurymerodesmidae. Prior supraspecific classification is in part inconsistent with the phylogeny and convergent evolution has caused artificial genera to be proposed. Subspecific classification is likewise incongruent with phylogeny and subspecies are consistently not sister to conspecifics. The phylogeny is used as a basis to update the classification of the family, diagnose monophyletic groups, and to inform species hypotheses.