In order to evaluate the diversity, endemism, distribution and conservation of the genus Euphorbia in SW Asian countries, we generated an updated and annotated checklist of 249 taxa belonging to the current accepted four Euphorbia subgenera, 30 sections and five subsections, based on floristic compilations followed by extensive verification of nearly 24,000 herbarium vouchers from the region. We also provide updated distribution maps for 247 of the 249 taxa treated. The predominant group is Euphorbia subg. Esula, with 19 sections and 184 taxa (176 species), followed by subg. Chamaesyce (six sections, 32 species), subg. Euphorbia (two sections, 21 species) and subg. Athymalus (three sections, 12 species). Turkey, Iran and Syria are the most diverse countries, with 102, 92 and 50 species, respectively. The richest concentration of Euphorbia species in SW Asia are the eastern part of the Mediterranean region in Lebanon with 27–34 taxa; Alborz, Zagros (Iran), Lesser Caucasus, and Anti-Taurus (S Turkey) with 21–27 taxa each are the second richest areas. The highest number of endemics occurs in Iran (21 taxa), followed by Turkey (12 taxa) and Yemen (7 taxa). All 134 endemic and subendemic taxa were evaluated by the IUCN Red List categories and criteria. Among the known Euphorbia species in the region, 10 of them (4.4%) are adventive. Life-form spectra show that the majority of species (80.7%) are hemicryptophytes, therophytes and chamaephytes. Twelve new records are reported here for Iran, Afghanistan, Oman, Pakistan, Qatar and Turkey, six synonyms and three sectional transfers are suggested.