Malpighiaceae has undergone unprecedented changes in its traditional classification in the past two decades due to several phylogenetic studies shedding light on the non-monophyly of all subfamilies and most tribes and genera. Even though morphological characters were used to reconstruct the last molecular generic phylogeny of Malpighiaceae, a new classification system has never been proposed for this family. Based on a comprehensive review of the last twenty years of published studies for this family, we propose a new classification system and provide a taxonomic synopsis for Malpighiaceae based on molecular phylogenetics, morphology, palynology, and chemistry as a baseline for the systematics, conservation, and taxonomy of this family worldwide. Malpighiaceae currently comprises two subfamilies (Byrsonimoideae and Malpighioideae), 12 tribes (
Acmanthereae
, Acridocarpeaetrib. nov., Barnebyeaetrib. nov., Bunchosieaetrib. nov., Byrsonimeae, Galphimieae, Gaudichaudieae, Hiptageae, Hiraeeae, Malpighieae, Mcvaughieaetrib. nov., and Ptilochaeteaetrib. nov.), 72 genera (incl. Mamedeagen. nov.), and 1,499 accepted species (715 of which are currently under some kind of extinction threat). We present identification keys for all subfamilies, tribes, and genera, a full morphological description for the proposed new genus, the re-circumscription of ten genera alongside the needed new combinations, the proposition of several new synonyms, the typification of several names, and notes on the taxonomy, distribution, conservation, and ecology up to the genus rank. Morphological plates are also provided to illustrate the immense diversity of morphological traits used in the new classification and synopsis.