New generic circumscriptions of the Paleotropical tribe Vanguerieae in the subfamily Ixoroideae s.l. (Rubiaceae) have recently been established as a result of a series of phylogenetic studies conducted by Lantz and Bremer. The genus Canthium Lam. was shown in their study to be highly polyphyletic, and a largely dioecious group was for the first time identified within Vanguerieae. The dioecious group sensu Lantz and Bremer comprises about 140 species classified in eight genera: Canthium (Canthium subg. Bullockia Bridson), Dinocanthium Bremek., Leroya Cavaco, Neoleroya Cavaco, Peponidium (Baill.) Are`nes, Pseudopeponidium Homolles ex Are`nes, Pyrostria Comm. ex Juss., and Scyphochlamys Balf. f. We sequenced 79 Vanguerieae taxa and performed phylogenetic analyses based on sequence data from two nuclear (ETS and ITS) markers to: (1) pinpoint the phylogenetic positions of the Comorean and Indian Ocean Canthium and the Southeast Asian Canthium confertum Korth. group in Vanguerieae; (2) evaluate the phylogenetic utility of three taxonomic characters (bract type, locule number, and fruit shape) previously and currently used for delimiting genera in the dioecious group; and (3) assess the evolution of functional dioecy in Vanguerieae. The results support a further disintegration of Canthium s.l., as the Comorean and Malagasy Canthium species are shown for the first time to be closely related to Peponidium. Similarly, C. confertum appears to have a close affinity with Cyclophyllum Hook. f. The combined analyses show that the dioecious group can be subdivided into four morphologically distinct clades formally recognized as genera: Bullockia (Bridson) Razafim., Lantz & B. Bremer, here elevated from Canthium subgen. Bullockia Bridson, as well as Cyclophyllum, Peponidium (including all Comorean, Malagasy, and Seychellean Canthium species), and Pyrostria (including Dinocanthium, Leroya, Neoleroya, Pseudopeponidium, and Scyphochlamys). All described species of Canthium subgen. Bullockia are transferred to Bullockia: B. dyscriton (Bullock) Razafim., Lantz&B. Bremer, B. fadenii (Bridson) Razafim., Lantz&B. Bremer, B. impressinervia (Bridson) Razafim., Lantz & B. Bremer, B. mombazensis (Baill.) Razafim., Lantz & B. Bremer, B. pseudosetiflora (Bridson) Razafim., Lantz & B. Bremer, and B. setiflora (Hiern) Razafim., Lantz & B. Bremer. Furthermore, the results seem to point to a single origin of functional dioecy followed by subsequent reversals back to the hermaphroditic conditions at least within the Cyclophyllum–Canthium confertum clade and Pyrostria s.l. The Malagasy Bullockia species seem to have an African ancestor, whereas the Comorean Peponidium and the African Pyrostria appear to have originated from Malagasy progenitors.