Phylogenetic relationships of Orthalicoidea, a highly diverse and dominant element in the Neotropics, were studied using nuclear and mitochondrial DNA sequences (ITS2/28S, CO1, H3). Specimens of various locations from the Southern Hemisphere (South America, Africa, Australia, New Zealand, Solomon Islands) were analysed (74 taxa, representing 30 genera). Our results support previously presented hypotheses, but also give surprises in terms of unexpected topologies. Phylogenetic trees were estimated using maximum likelihood and Bayesian inference, and compared with traditional classifications. Phylogenetic estimations using three loci gave a strong support for monophyly of Orthalicoidea, as well as for some clades within this group (Bulimulidae, Bothriembryontidae, Orthalicidae, Amphibulimulidae), but not for others (Odontostomidae and Megaspiridae). In the resulting revision of the classification scheme of the Orthalicoidea, the tribe Simpulopsini is raised to family rank. One new subfamily is recognized, the Bostrycinae. The family Bulimulidae Tryon 1867 is retained under ICZN Art. 35.5, despite the senior synonymy of Peltellinae Gray 1855. Our analysis supports an origin of the Orthalicoidea in South America, with subsequent radiations into other parts of the Neotropics and the Southern Hemisphere. The hypothesis that the distribution on the southern continents may be explained by vicariance due to break-up of Gondwana is only partially supported by divergence time analysis using fossil calibrations. Ancestral area reconstruction suggests various independent dispersals out of South America into Central America and the West Indies, and possibly two independent dispersals to explain the remaining relations between groups of taxa on the southern continents. Divergence time analysis further shows that the major diversification of extant taxa within the superfamily may have started around the Cretaceous-Paleogene boundary. © E. Schweizerbart'sche Verlagsbuchhandlung (Nägele u. Obermiller), 2012.