Ochnaceae s.l. is a family of trees, shrubs or rarely herbs widely distributed in tropical and subtropical forests and savannas of the Old and New World, and has about 500 species in 32 genera. The family is divided into three subfamilies: Medusagynoideae, Quiinoideae and Ochnoideae. We have provided, for the first time, a nearly complete molecular phylogenetic analysis of Ochnaceae s.l. resolving most of the phylogeny backbone of the family using five DNA regions. Based on this, dating analyses were performed using a secondary calibration, and relaxed molecular clock models. The historical biogeography of Ochnaceae s.l. was reconstructed using Dispersal-Vicariance Analysis and Bayesian Binary MCMC. The Neotropics were inferred as being the geographical origin of the family and the Old World was most likely colonized via the North Atlantic Land Bridge during a period when climatic conditions allowed establishment of a boreotropical flora. A full taxonomic revision of the continental African species of the genus Campylospermum has been prepared and additional historical biogeographic analyses were performed with a focus on the genus Campylospermum.