Tribe Crotalarieae is a large and diverse group of papilionoid legumes that largely occur in Africa. A systematic study of generic relationships within the tribe was undertaken using nucleotide sequences from the internal transcribed spacer (ITS) of nuclear ribosomal DNA, the plastid gene rbcL, and morphological data. The Crotalarieae are supported strongly as monophyletic and sister to the tribe Genisteae. Lebeckia, Lotononis, and Wiborgia are all paraphyletic in the molecular analyses and morphological data support the division of Lebeckia into three more natural genera (one of which includes the monotypic North African Spartidium). Four major lineages were identified within the tribe based on sequence data: the “Cape” group, comprising Aspalathus, Lebeckia, Rafnia, Spartidium, and Wiborgia; the Lotononis group, comprising Lotononis pro parte, Pearsonia, Robynsiophyton, and Rothia; a group comprising Lotononis section Leptis, L. section Listia, and allies; and the Crotalaria group, comprising Bolusia, Crotalaria, and Lotononis hirsuta (Lotononis section Euchlora). Morphological analysis yields a similar topology, except that Lotononis is monophyletic if L. hirsuta were excluded. When the molecular and morphological data sets are combined, the same major clades are retrieved as in the molecular analysis, with the notable exception that Lotononis and Lebeckia senso stricto are supported as monophyletic. The results from this study have important implications for the classification of the tribe Crotalarieae and present an important step towards a natural and phylogenetic generic classification for the tribe.