AbstractOpiliaceae are a pantropical family of the Santalales mainly distributed in the Old World with only one genus in the neotropics. Opiliaceae have remained taxonomically unresolved and the generic relationships within the family have been disputed. Here we present molecular phylogenetic analyses of the family and its close relatives using a combined dataset of the nuclear ribosomal (small subunit rDNA and large subunit rDNA) and the chloroplast rbcL, matK, and trnL‐F regions. We also carried out a morphological phylogenetic analysis using 24 characters for all the species of Opiliaceae and three species in Santalaceae s.l. and Strombosiaceae as outgroups. Molecular analyses strongly supported the monophyly of Opiliaceae. Agonandra Miers ex Benth. & Hook. f. is sister to all the other genera of Opiliaceae. The remaining genera form two major clades: the Opilia clade (including Cansjera Juss., Lepionurus Blume, Opilia Roxb., Pentarhopalopilia (Engl.) Hiepko, Rhopalopilia Pierre, and Urobotrya Stapf.), and the other consisting of Anthobolus plus the Champereia clade (including Champereia Griff., Melientha Pierre, and Yunnanopilia C. Y. Wu & D. Z. Li). We propose a new classification of Opiliaceae, recognizing 12 genera and four tribes, with the description of a new tribe, Champereieae Bing Liu, C. T. Le, L. M. Lu & Z. D. Chen.