A large, combined phylogenetic analysis (including morphological and molecular data from 18S rDNA, 16S rDNA and cytochrome c oxidase subunit I), with the highest number of species and genera of Syllidae studied to date (213 terminals), is examined. The data were explored with different parameters and optimality criteria (parsimony, likelihood, and bayesian inference). The monophyly of Syllidae and most of the traditional subfamilies is supported. The subfamily Eusyllinae is polyphyletic, as currently delineated, but it is herein reorganized and its diagnosis modified to be a valid group. Additional well supported clades arise. The phylogenetic relationships of the well known and established genera, as well as several enigmatic genera (e.g. Anguillosyllis, Paraopisthosyllis and Parahaplosyllis), the position of which in syllid taxonomy was uncertain or dubious to date, are clarified. The results corroborate previous hypotheses about the evolution of the reproductive and brooding modes. Within Syllinae, the nature of the stolon is phylogenetically informative. The classification of the whole family is revised and discussed on the basis of this phylogenetic hypothesis.© The Willi Hennig Society 2011.