Miniaturization has evolved numerous times and reached impressive extremes in the Anura. I compared the skeletons of miniature frog species to those of closely related larger species to assess patterns of morphological change, sampling 129 species from 12 families. Two types of morphological data were examined: (1) qualitative data on bone presence and absence; and (2) thin-plate spline morphometric descriptions of skull structure and bone shape. Phylogenetic comparative methods were used to address the shared history of species. Miniature anurans were more likely to lose skull bones and phalangeal elements of the limbs. Their skulls also showed consistent differences compared to those of their larger relatives, including relatively larger braincases and sensory capsules, verticalization of lateral elements, rostral displacement of the jaw joint, and reduction of some skull elements. These features are explained by functional constraints and by paedomorphosis. Variation among lineages in the morphological response to miniaturization was also explored. Certain lineages appear to be unusually resistant to the morphological trends that characterize miniature frogs as a whole. This study represents the first large-scale examination of morphology and miniaturization across a major, diverse group of organisms conducted in a phylogenetic framework and with statistical rigor.