Protodrilidae is a group of small, superficially simple-looking annelids, lacking chaetae and appendages, except for two prostomial palps. Originally considered to be one of the primitive "archiannelid" families, its affinity within Annelida is still highly debated. Protodrilids are found worldwide in the interstices of intertidal and subtidal marine sediments. Despite their simple appearance they constitute one of the most species-rich interstitial families, with 36 described species in two genera, Protodrilus and the gutless Astomus. Here we present the first phylogenetic study of Protodrilidae employing five gene fragments, 55 morphological characters and 73 terminals (including seven outgroups) analysed under direct optimization and parsimony as well as model-based methods. The large data set includes all 36 described species of Protodrilidae (17 of which are represented only by the morphological partition) as well as 30 undescribed or uncertain species (represented by both morphology and molecules). This comprehensive, inclusive and combined analysis revealed a new perspective on the phylogeny of Protodrilidae: the family is shown to contain six cosmopolitan subclades, each supported by several morphological apomorphies, and with the genus Astomus consistently nested among the other five clades rather than next to these. Consequently, the diagnosis of Protodrilus is emended, Astomus remains unchanged and the four remaining lineages are diagnosed and named Megadrilus n. gen, Meiodrilus gen. nov., Claudrilus n. gen and Lindrilus gen. nov. Character transformations showed that large size and presence of pigmentation, oviducts and eyes are plesiomorphies of the family, retained in Protodrilus, Megadrilus gen. nov. and Lindrilus gen. nov. These features are secondarily lost in the gutless Astomus with epidermal uptake of nutrients, as well as in Meiodrilus gen. nov. and some species of Claudrilus n. gen, with smaller size correlated to life in interstices of finer sediments.