Based on sequence data of the nuclear ITS and plastid matK, trnL-F and psbA-trnH markers of 162 species (169 accessions), the relationships and monophyly of tribe Hedysareae and its close relatives were assessed, with special reference to the infrageneric phylogeny of Hedysarum. The results showed that Hedysareae sensu Lock is not monophyletic, and its relationships with tribe Galegeae are unclear. Tribe Galegeae is polyphyletic. Hedysareae sensu Lock includes two strongly supported clades: the Caraganean clade and the Hedysaroid clade. Tribe Caraganeae Ranjbar was supported to be recognized based on the Caraganean clade, but it is herein suggested to be re-circumscribed by excluding Chesneya and Gueldenstaedtia. Our results support treating the Hedysaroid clade as tribe Hedysareae, comprising nine genera: Alhagi, Corethrodendron, Ebenus, Eversmannia, Greuteria, Hedysarum, Onobrychis, Sulla and Taverniera. Hedysarum as delimited here consists of three main clades: the first clade (the mesic group) corresponds to H. sect. Hedysarum; the second clade (the xeric group) is the re-defined H. sect. Multicaulia, consisting of the core group of H. sect. Multicaulia plus the former genus Sartoria; and the third clade (the psychrophilic group) includes the monospecific H. sect. Stracheya (with H. tibeticum) and two species previously placed in H. sect. Multicaulia (H. kumaonense, H. lehmannianum).