Within the large family Asteraceae (23,000 species), Melampodium, containing 40 species, belongs to the Heliantheae Alliance, tribe Millerieae. The genus is characterized by radiate heads, 3–5 outer involucral bracts (phyllaries), envelopment of the female, fertile ray achenes by the inner series of morphologically variable phyllaries, and functionally male disc florets, rendering the entire capitulum monoecious. Species of Melampodium are mainly distributed in Mexico with extensions north into the southwestern United States and south into Central and northern South America (including disjunctions in Brazil). In Mexico, species inhabit many vegetation types, including pine-oak forests, evergreen and deciduous tropical forests, mesquite-grassland, desert, thorn forest, and savanna. Melampodium contains a wide diversity of secondary plant metabolites, especially sesquiterpene lactones, including melampolides. Extensive chromosomal diversity occurs within Melampodium with n = 9, 10, 11, 12, 14, 18, 20, 23, 24, 27, 28, 30, and 33. This broad range of cytological variation makes the genus unique within the family, especially the Heliantheae Alliance. Two species of Melampodium have entered the horticultural trade, M. divaricatum and M. montanum.