Species of the genus Pleurodema are relatively small, plump frogs that mostly occur in strong‐seasonal and dry environments. The genus currently comprises 14 species distributed from Panama to southern Patagonia. Here we present a phylogenetic analysis of Pleurodema, including all described species and several outgroups. Our goals include testing its monophyly and the monophyly of the species groups that were historically proposed, and studying the evolution of some character systems, particularly macroglands and egg‐clutch structure; this last point also provided the chance for a discussion of foam nest evolution in anurans. Our dataset includes portions of the mitochondrial genes cytochromeb, 12S, 16S, and the intervening tRNAVal; the nuclear gene sequences include portions of rhodopsin exon 1 and seven in absentia homolog I. Our results support a clade composed of Pleurodema and including the monotypic SomuncuriaLynch, 1978 nested within it. The latter genus is therefore considered a junior synonym of Pleurodema and its sole species is added to this genus. Furthermore, our results indicate the non‐monophyly of several species groups proposed previously. We recognize four clades in Pleurodema: the P. bibroni clade (P. bibroni, P. cordobae and P. kriegi), the P. thaul clade (P. bufoninum, P. marmoratum, P. somuncurensis and P. thaul), the P. brachyops clade (P. alium, P. borellii, P. brachyops, P. cinereum, P. diplolister and P. tucumanum) and the P. nebulosum clade (P. guayapae and P. nebulosum). Our results further indicate the need for a taxonomic reassessment of P. borellii and P. cinereum (as did previous studies), P. guayapae and P. nebulosum, and the three species in the P. bibroni clade. Pleurodema shows a striking pattern of variation in presence/absence of lumbar glands. Our results indicate multiple losses or independent gains of this character associated with defensive displays. The reproductive modes of Pleurodema include four different egg‐clutch structures. The optimization of these indicates that there are at least two independent transformations from the plesiomorphic mode of foam nests to egg‐clutch structures involving gelatinous masses of different sorts (ovoid plates, masses, or strings). We hypothesize that these independent transformations could involve changes at the behavioural (the loss of foam beating behaviour by the parent) and/or structural level (transformations involving the pars convoluta dilata, the section of the oviduct where the foam‐making substance is secreted). Finally, our study of foam nest evolution in Pleurodema is extended to the other groups of anurans where foam‐nesting occurs, on the basis of available data and recent phylogenetic hypotheses. In the different hyloid groups where it occurs, foam‐nesting evolved from clutches laid in water. However, in all ranoids in which foam‐nesting occurs, it evolved from terrestrial clutches, with eggs laid hanging in vegetation, or, if the clutches are laid on a restricted volume of water, involving endotrophic develop...