Abstract The Saturniidae, or wild silkmoths, number approximately 1861 species in 162 genera and nine subfamilies including Cercophaninae and Oxyteninae. They include some of the largest and most spectacular of all Lepidoptera, such as the moon or luna moths, atlas moths, emperor moths, and many others. Saturniids have been important as sources of wild silk and/or human food in a number of cultures, and as models for comparative studies of genetics, development, physiology, and ecology. Seeking to improve the phylogenetic framework for such studies, we estimated relationships across Saturniidae, sampling all nine subfamilies plus all five tribes of Saturniinae. Seventy-five exemplars (45 Saturniidae plus 30 bombycoid outgroups) were sequenced for four protein-coding nuclear gene regions (5625 bp total), namely CAD (the fusion protein carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase), DDC (dopa decarboxylase), period, and wingless. The data, analyzed by parsimony and likelihood, gave a strongly resolved phylogeny at all levels. Relationships among subfamilies largely mirrored the pre-cladistic hypothesis of Michener, albeit with significant exceptions, and there was definitive support for the morphology-based proposal that Ludiinae form a tribe (Micragonini) within Saturniinae. In the latter subfamily, the African tribe Urotini was shown to be paraphyletic with respect to Bunaeini and Micragonini, also in accord with recent morphological findings. Relationships within the New World subfamilies Arsenurinae, Ceratocampinae and Hemileucinae nearly always accord with previous morphology-based phylogenies when both are clearly resolved. Within Hemileucinae, Hemileucini are paraphyletic with respect to the monotypic Polythysanini. A preliminary biogeographical analysis supports ancestral restriction to the New World, followed by dispersal and/or vicariance splitting most of the family into a largely New World versus a largely Old World clade.