A first approximation of evolutionary relationships within the Asclepiadinae (Apocynaceae: Asclepiadoideae) is inferred from two DNA data sets, from the nuclear ITS region, and from plastid trnT-L and trnL-F spacers and trnL intron. Both the subtribe as a whole and the phylogenetic radiation of largely herbaceous genera around Asclepias are monophyletic and well supported. While resolution within the Asclepias complex is limited, the lineages identified demonstrate that current generic delimitation is unsatisfactory. Asclepias should be either restricted to New World members of the subtribe or expanded to encompass the entire radiation. In the African species, it is shown that, although the corona is taxonomically important for recognizing species, it can be misleading as an indicator of phylogenetic relationship. Vegetative similarities often prove a more reliable guide, but more detailed studies are needed to refine these lineages and to detect morphological characters to aid in their practical recognition.