Tridimeris is the only genus of Annonaceae endemic to Mexico, and since its description more than 150 years ago, the genus has been largely ignored. Here, based on herbarium specimens and a comprehensive phylogenomic study involving hundreds of nuclear markers, the first taxonomic revision of the genus Tridimeris (Annonaceae, Malmeioideae, subtribe Sapranthinae) is presented. Ten species are recognized, six of which are newly described here. All the species are exclusively found in Mexico's most humid forests, particularly in the montane cloud forest and the tropical rainforest. The genus Tridimeris is morphologically distinguished from other neotropical genera of the Annonaceae by its leaves with pocket domatia present in the axils of the secondary veins, by its dimerous flowers (two sepals and four petals), basally fused sepals with ciliated margins, by a reduced number of carpels per flower (1–5) and by its large and fleshy fruits (monocarps) with numerous seeds. A highly resolved phylogenetic hypothesis provides strong support for the relationships among Tridimeris species, forming two well-supported clades. Consequently, two new sections are proposed, namely Tridimeris sect. Tridimeris and Tridimeris sect. Zoque. A detailed description of the morphology of the genus is presented, including the description of the pollen, domatia and its phylogenetic relationships. Taxonomic treatments of the species include synonyms, geographic and ecological notes, comparisons with similar species and a preliminary assessment of their conservation status. All species of the genus are potentially threatened with extinction and eight are assessed as Critically Endangered, which makes it the most threatened lineage of Mexican trees. This study emphasizes the importance of scientific collections as invaluable sources of data for current taxonomic revisions and conservation. It is a formal invitation to preserve and support the basic scientific research.