Asteridae, comprising about one-third of all angiosperm species, include almost all species that produce iridoids and that have sympetalous corollas, and most species that have unitegmic-tenuinucellate ovules. To elucidate their phylogeny, we used separate and combined data sets of sequences from 18S rDNA, rbcL, ndhF, and atpB, with a maximum of 7168 base pairs for 158 genera, for phylogenetic analysis. The analyses resolved the major lineages of Asteridae s.l., confirming the feasibility of analyses of large data sets in phylogenetic systematics. Most of the taxa fall within one of four major clades. Cornales, comprising Cornaceae, Nyssaceae, Hydrangeaceae, Loasaceae, and Hydrostachyaceae, are sister to the remaining genera. Ericales consist of taxa traditionally included in Ericales, Primulales, Ebenales, and Theales, as well as Polemoniaceae and Balsaminaceae. They are sister to euasterids I and euasterids II. The euasterids II comprise Asterales, Apiales, Dipsacales, Escallonia, Eremosyne, and Berzelia, and Aquifoliales. Dipsacales, including Sambucus and Viburnum, are monophyletic and sister to Apiales. The euasterids I include Lamiales, Boraginaceae, Solanales, and Gentianales. The relationship of Boraginaceae as sister to Lamiales, even though weakly supported, is reported for the first time. The data set of 158 taxa sequenced for four genes gives us insight into both the evolution of the Asteridae and the molecular evolution of the four genes. Some striking differences in rates and patterns of molecular evolution appear both within and among the genes; for example, ndhF consists of two very different regions with the second region apparently evolving under reduced selection pressure. The four genes differ in their base composition, transition-transversion bias, and in their most common substitutions.