On the basis of multidisciplinary studies on the tribe Rubieae, we contribute to the current discussion on paraphyly and supraspecific taxa that do not contain all descendant species of an ancestral clade. Rubieae belong to the large, predominantly tropical and woody family Rubiaceae and include possibly ≤ 1000 mostly temperate and herbaceous species with worldwide distribution. Our studies span distinctive groups throughout the tribe, consist of a maximum parsimony analysis of plastid atpB-rbcL and rpL32-trnL DNA sequences, and are summarized in a condensed strict consensus tree. A corresponding two-dimensional scheme illustrates alternative hypotheses for phylogenetic relationships among all major Rubieae clades identified. The small relictual genus Kelloggia Torr. in Benth. & Hook. f., formerly excluded from the Rubieae, is supported as a remnant of the ancestors of the tribe. Didymaea Hook. f. and Rubia L. represent early phylogenetic side lines. All other Rubieae form a large monophyletic crown group with the traditional genera Asperula L. being polyphyletic and Galium L. paraphyletic. Changes in the circumscription of these and other genera are thus inevitable. The necessity of accepting paraphyletic taxa as well as the positive and negative aspects of taxonomic splitting versus lumping within Rubieae are discussed. Additionally, lectotypes are designated for one section of Asperula---Asperula sect. Dioicae Airy Shaw & Turrill, typified by A. conferta Hook. f.—and for three sections of Galium---Galium sect. Leiogalium (DC.) Ledeb., typified by G. sylvaticum L.; Galium sect. Lophogalium K. Schum., typified by G. multiflorum Kellogg; and Galium sect. Depauperata Pobed., typified by G. songaricum Schrenk ex Fisch. & C. A. Mey.