The class Myxomycetes consists of free-living protists characterised by their complex life cycle, which includes both microscopic (amoebae, flagellates and cists) and macroscopic stages (spore-bearing fruiting bodies, sclerotia, and plasmodia). Within it, the order Physarales, with more than 450 recognised species, constitutes the largest group. Although previous studies have shown the polyphyly of some of the traditionally accepted genera, its internal phylogenetic relationships have remained uncertain so far, and together with the lack of data for some key species, it prevented any taxonomic and nomenclatural revisions. We have compiled a substantially expanded dataset in terms of both taxon sampling and molecular data, including most of the genera described to date and four unlinked DNA regions, for which we provide partial sequences: nSSU, EF-1α, α-Tub, and mtSSU, analysed through maximum likelihood and Bayesian methods. Our results confirm that the family Didymiaceae is paraphyletic to the rest of Physarales. Within Didymiaceae s.lat., the recent reinstatement of the genus Polyschismium for most species traditionally ascribed to Lepidoderma, except for the type (Ronikier et al. 2022), is further supported here, as well as the definite inclusion of the genus Mucilago in Didymium and Lepidoderma s.str. (L. tigrinum) in Diderma (Prikhodko et al. 2023). Additionally, the genus Diachea is redefined to include some species previously treated in Physaraceae (Craterium spp. with true columella). Within the monophyletic family Physaraceae, most genera are recovered as polyphyletic, suggesting that they should be no longer accepted as currently defined. However, the lack of resolution of some relationships within Physaraceae prevents us from resuscitating or creating several new genera to mitigate polyphyly. Among the well-defined groups with clear molecular signatures, we propose two taxonomic and nomenclatural changes at generic level: 1) a new genus, Nannengaella, is proposed for a major clade containing Physarum globuliferum and other species with heavily calcified sporophores and, often, a true calcareous columella; 2) Lignydium is resurrected for the clade containing Fuligo muscorum. Additionally, Trichamphora is suggested as the correct name for the clade containing Physarum pezizoideum. The taxonomy and nomenclature of some provisional genera, currently synonymous with Fuligo and Physarum, are disentangled, and we provide a comprehensive and updated nomenclatural conspectus that can be used when better resolved phylogenies are obtained. In total, 22 new combinations are proposed in different genera. A provisional key to the genera of the order is also provided.