In an attempt to elucidate relationships among the morphologically diverse members of Saxifragaceae sensu lato, phylogenetic analyses of rbcL sequence data were conducted on representative genera of 16 of the 17 subfamilies. Also included were many putatively related families, as well as a diverse array of dicotyledonous flowering plants. Our phylogenetic analyses suggest that taxa of Saxifragaceae sensu lato are allied with at least 10 separate, often distantly related, lineages of several subclasses of flowering plants. Sequence data, in combination with other lines of evidence, suggest that Saxifragaceae sensu stricto should consist only of subfamily Saxifragoideae, a group of about 30 herbaceous genera that form the core of Saxifragaceae sensu lato. These data also suggest that potential close relatives of Saxifragaceae sensu stricto include Iteoideae, Pterostemonoideae, and Ribesoideae and possibly Penthoroideae and Tetracarpaeoideae, all traditional subfamilies of Saxifragaceae sensu lato, as well as Crassulaceae. These members of Saxifragaceae sensu lato, along with Saxifragaceae sensu stricto, Crassulaceae, and several genera from the subclass Hamamelidae, are basal to a large assemblage of taxa, most of which are usually placed in Rosidae. Within this primarily rosid alliance, representatives of four other subfamilies of Saxifragaceae sensu lato (Francooideae, Baueroideae, Parnassioideae, and Lepuropetaloideae) are allied with the rosid families Greyiaceae, Cunoniaceae, and Celastraceae. According to rbcL sequence evidence, Hydrangeoideae and Cornaceac are closely related members of a clade that is basal to a large group of taxa primarily from subclass Asteridae. Representative genera of four subfamilies of Saxifragaceae sensu lato (Phyllonomoideae, Escallonioideae, Montinioideae, and Vahlioideae) are in our results allied with taxa usually included in Asteridae. Significantly, relationships of Saxifragaceae sensu lato suggested by rbcL sequence data are in very close agreement with those supported by several other lines of evidence, especially embryology, serology, and iridoid chemistry.