The worldwide distributed neogastropod family Muricidae comprises more than 1800 extant species of whelks, rock-shells, murex-shells, drill-shells, and coral-shells. Despite several attempts at a taxonomic revision based on morphological characters, the systematics of this family is still largely debated. Here, we present a molecular revision of the family Muricidae based on the largest dataset analysed so far, which comprises 384 specimens representing 360 species and includes, for the first time, all the currently recognised subfamilies. A molecular dataset of cox1, 12S rRNA, 16S rRNA, and 28S rRNA genetic markers and six fossil-based calibration points were used to produce time-calibrated phylogenetic reconstructions, using a Maximum Likelihood approach. Our results confirmed the monophyly of most of the accepted subfamilies, suggested a revision of the taxonomic composition of Muricopsinae and Muricinae, and highlighted some lineages not immediately comprised in any of the recognised subfamilies. The origin and early diversification of the subfamilies of Muricidae occurred between 32 and 60 million years ago.