Phylogenetic relationships are often poorly understood at higher taxonomic levels (family and above) despite intensive morphological analysis. An excellent example is Saxifragaceae sensu lato, which represents one of the major phylogenetic problems in angiosperms at higher taxonomic levels. As originally defined, the family is a heterogeneous assemblage of herbaceous and woody taxa comprising 15 subfamilies. Although more recent classifications fundamentally modified this scheme, little agreement exists regarding the circumscription, taxonomic rank, or relationships of these subfamilies. The recurrent discrepancies in taxonomic treatments of the Saxifragaceae prompted an investigation of the power of chloroplast gene sequences to resolve phylogenetic relationships within this family and between the Saxifragaceae and other major plant lineages. Sequence data from the gene rbcL (ribulose-1,5-bisphosphate carboxylase, large subunit) reveal that (i) Saxifragaceae sensu lato is at least paraphyletic, and probably polyphyletic, (ii) the genera Parnassia and Brexia are only distantly related to other members of Saxifragaceae, and (iii) representatives of the Solanaceae (subclass Asteridae) appear more closely related to Saxifragaceae (subclass Rosidase) than traditionally maintained. These data illustrate the value of chloroplast gene sequence data in resolving genetic, and hence phylogenetic, relationships among members of the most taxonomically complex groups.