A monographic study of the family Anisophylleaceae in the order Cucurbitales was carried out. Four genera, Anisophyllea (67 spp.), Combretocarpus (1 sp.), Poga (1 sp.), and Polygonanthus (2 spp.), and together 71 species are recognized, of which 18 are described as new. The 18 new species are all in Anisophyllea and include A. bakoensis, A. biokoensis, A. borneensis, A. cuneata, A. dinghoui, A. glandibeccariana, A. glandulipetiolata, A. insularis, A. malayensis, A. myriostictoides, A. neopurpurascens, A. obanica, A. rengamensis, A. rubroglandula, A. sabahensis, A. sarawakensis, A. sessiliflora, and A. sumatrana. Keys to the genera and to species of Anisophyllea and to those of Polygonanthus are provided. All species are described in detail and all but two are illustrated. Information on their distribution and habitat, phenology, and vernacular name and local usage, if available, is given. Distribution map of every species is presented. Taxonomic history, taxonomic characters, and various taxonomic issues are discussed. We also lectotypify or neotypify 30 names in the family including Anisophyllea apetala Scortechini ex King, A. beccariana Baillon, A. boehmii Engler, A. brachystila Engler & von Brehmer, A. buettneri Engler, A. cabole Henriques, A. cordata Engler & von Brehmer, A. curtisii King, A. exellii P. A. Duvigneaud & Dewit, A. fissipetala Engler & von Brehmer, A. fruticulosa Engler & Gilg, A. gaudichaudiana Baillon, A. gossweileri Engler & Brehmer, A. griffithii Oliver, A. guianensis Sandwith, A. mayumbensis Exell, A. meniaudi Aubréville & Pellegrin, A. obtusifolia Engler & Brehmer, A. poggei Engler ex De Wildeman & T. Durand, A. pomifera Engler & Brehmer, A. purpurascens Hutchinson & Dalziel, A. scortechinii King, A. sororia Pierre, A. strychnoides Engler & Brehmer, A. tomentosa Rolfe, A. trapezoidalis Baillon, A. zeylanica Bentham, Combretocarpus motleyi J. D. Hooker, Macrosolen rotundatus Miquel, and Poga oleosa Pierre.