Hedyotis and related genera (here called the Hedyotis-Oldenlandia complex) are highly debated groups in the Rubiaceae family with no consensus to date on their generic delimitations. The present study focuses on Asian-Pacific taxa from these groups and aims at resolving taxonomic inconsistencies by describing monophyletic genera within the complex. The generic circumscriptions presented in our study are based on the phylogenetic trees of nuclear (ITS, ETS) and plastid (petD, rps16) sequence data inferred using Bayesian and maximum likelihood methods. Morphological key features of the group such as habit, fruit type, seed form, and pollen type are studied and compared with the phylogeny to characterize the clades. Based on these results, the Asian-Pacific members are placed in 14 monophyletic groups across the Hedyotis-Oldenlandia complex. Of these, we accept and circumscribe 13 monophyletic genera: Debia, Dentella, Dimetia, Edrastima, Exallage, Hedyotis, Involucrella, Kadua, Kohautia, Leptopetalum, Neanotis, Oldenlandia, and Scleromitrion. Two of these, Debia and Involucrella, are here described as new genera.