Mesoamerica is the geographic region between northern México and southern Panamá. This region shows specific cultural and biological features, both presently and in the past. The proboscideans (Mammalia, Proboscidea) that inhabited the region in a time range from middle Miocene to late Pleistocene are outlined. Three families (Elephantidae, Gomphotheriidae, and Mammutidae) and six genera currently are known from the region. The systematic position of the genus Stegomastodon is unresolved, whether monophyletic or paraphyletic, and it may include two genera, Stegomastodon sensu stricto and Haplomastodon. The other five genera recognized for the region are Gomphotherium (1 species), Rhynchotherium (3 species), Cuvieronius (3 species), Mammut (1 species), and Mammuthus (2 species). The Great American Biotic Interchange played an important role for the migration of the proboscideans into South America. The association between proboscideans and humans in Mesoamerica has been explored, but there is only evidence of an association with mammoths exists.