We infer phylogenetic relationships and test the monophyly of genera of the African Asclepias complex with three non-coding plastid DNA regions, rpl16 intron, trnC-rpoB spacer, and trnS-G spacer/trnG intron. We find that Asclepias (Trachycalymma) pseudofimbriata forms a polytomy with a clade of all other sampled African species of Asclepias s. l. and a clade of the American Asclepias s. s. Asclepias s. l. and the African species classified in Asclepias are both paraphyletic groups since segregate genera are all nested among species of African Asclepias. Most segregate genera are not monophyletic, i.e. Gomphocarpus, Pachycarpus, Stathmostelma, Xysmalobium, Schizoglossum, and Aspidoglossum; however, Glossostelma is monophyletic. Due in part to low levels of divergence in the sampled plastid markers, the approximately unbiased test did not reject the monophyly of the African species of Asclepias nor the segregate African genera, although the monophyly of Asclepias circumscribed to include American and African species but excluding currently recognized genera was rejected. Based on the results of this study, the species comprising the African Asclepias complex cannot be readily partitioned into monophyletic genera.