With ca. 1400 species, Begonia is one of the largest plant genera. To address the evolution of Begonia we have produced maximum parsimony cladograms for nuclear large subunit and internal transcribed spacer sequence data in combination with 34 informative morphological characters. Data were obtained from 64 species of Begonia, the monotypic genus Hillebrandia, and both species of Datisca. The resulting phylogenetic hypotheses supported three main clades within Begonia, two internally resolved clades of African plants, and one unresolved transcontinental clade containing species from southern Africa, America, Asia, and the Socotran archipelago. Morphological characters often support well-resolved molecular clades. Tepal number in the staminate and carpellate flowers and fruit characters are discussed. None of the morphological characters sampled, including traditionally emphasized characters in sectional delimitations such as locule number and number of placental branches, provides a basis for subdividing Begonia into easily circumscribed monophyletic groups. Implications for future sectional classifications of Begonia are discussed.