Cheilanthoid ferns have a worldwide distribution and are found in rocky and seasonally dry habitats. Difficulty in deciphering natural lineages of cheilanthoids has been attributed to morphological convergence associated with adaptation to xeric environments. The goal of this study was to investigate the monophyly of the genus Pellaea by generating a DNA sequence-based cheilanthoid phylogeny. DNA sequences of the chloroplast rps4 gene and rps4-trnS intergenic spacer (IGS) were generated from 105 exemplars; chloroplast trnL-F IGS sequences were also generated from 60 of these samples. Results show that Pellaea sensu Tryon and Tryon is polyphyletic; Pellaea sections Holcochlaena and Ormopteris are distant relatives of sections Pellaea and Platyloma and have closer relationships with Doryopteris. A monophyletic circumscription of “pellaeoid” ferns is here defined to include traditional P. sect. Pellaea, P. sect. Platyloma, Astrolepis, and elements of Paragymnopteris and Paraceterach, all of which form a clade sister to Argyrochosma. Several other novel systematic implications of cheilanthoid relationships are also presented. The distribution of base chromosome numbers across the cheilanthoid phylogeny reveals potential synapomorphies of x  =  29 for the pellaeoid clade and x  =  27 for Argyrochosma, and suggests a trend toward reduction in base number during cheilanthoid evolution. Current geographic distribution of cheilanthoid ferns suggests a history of multiple introductions into the Old World from several ancestral New World lineages.