Prestonia R. Br. (apocynoids, Echiteae) comprises ca. 58 species, which are lianas with eglandular leaves, axillary or terminal cymose inflorescences, sepals with a single colleter, flowers usually with an annular corona around the mouth and/or free corona lobes, follicular fruits, and truncate seeds that are comose at themicropylar end. Three infrageneric classifications have been proposed in the last 110 years, all of them based only on morphological characters and none of which have been tested with molecular data. In the present study, based on the analyses of 62 nuclear and 258 chloroplast sequences from 65 species, we test the monophyly of Prestonia as well as the infrageneric classifications proposed for the genus. Prestonia was shown to bemonophyletic, but the infrageneric sections proposed by Schumann, Woodson, and Pichon are all non-monophyletic. We propose a new infrageneric classification for Prestonia, recognizing six sections: Coalitae Woodson, Denticulatae J. F. Morales, M. E. Endress & Liede, Exsertae J. F. Morales, M. E. Endress & Liede, Haemadictyon (Lindl.) Baill., Mollis J. F. Morales, M. E. Endress & Liede, and Prestonia. A key to the sections is provided. Prestonia pickelii Markgr. is removed fromthe synonymy of P. quinquangularis (Jacq.) Spreng. and resurrected as an accepted species. We provide a brief overview of the prolific groundbreaking work of Robert E. Woodson and Marcel Pichon in the Apocynaceae and Prestonia, and respectfully pay homage to their invaluable contributions to our knowledge of the family.