With more than 100 species, Mecodium is the largest infrageneric taxon of Hymenophyllum s.l. It was long considered a natural and homogeneous group, but recent phylogenetic studies have questioned this assertion. Using rbcL, rbcL-accD, and rps4-trnS sequences, we demonstrate that Mecodium is highly polyphyletic. Several species of Mecodium form the derived clade “H. polyanthos”; one species is nested within a second derived clade; and the remaining species are assigned to five basal clades including taxa regarded as distantly related. These clades are strongly supported both by parsimony and Bayesian analyses, but the relative placement of the basalmost clades lacks support. We show that the members of “basal Mecodium” are characterized by features that are plesiomorphic for Hymenophyllum s.l.—a reduced or dorsi-ventral stele, a lamina generally at least partially thickened, and a chromosome number based on x = 36, whereas taxa in the “H. polyanthos” clade have a subcollateral stele, the one-cell thick lamina typical of the family, and x = 28. There is a high level of variation among the basal species, and, notably, the rhizome indumentum is shown to be an interesting character for distinguishing among the basal clades. These new findings stress the need for further studies on Hymenophyllum s.l., and reassessment of its classification.