Tarantula hawk wasps in the genera Pepsis and Hemipepsis are conspicuous elements of Southwestern U. S. and the Neotropics where they often appear oblivious to potential predators while they actively forage for nectar or search for prey. Tarantula hawks produce large quantities of venom and their stings produce immediate, intense, excruciating short term pain in envenomed humans. Although the instantaneous pain of a tarantula hawk sting is the greatest recorded for any stinging insect, the venom itself lacks meaningful vertebrate toxicity. The respective lethalities of 65 and 120 mg/kg in mice for the venoms of Pepsis formosa pattoni and P. thisbe reveal that the defensive value of stings and venom of these species is based entirely upon pain. This pain confers near absolute protection from vertebrate predators. The pain also forms an enabling basis for the evolution of aposematic coloration, aposematic odor, and a huge mimicry complex involving most species of tarantula hawks and numerous flies, beetles, moths, acridid grasshoppers, and other Hymenoptera. Tarantula hawks form mixed-species, both-sex aggregations that appear defensive in nature and likely aid in the location of resources and mating opportunities for some species. Because tarantula hawks have no meaningful predators, selection pressure appears to have favored long life spans. Long-lived individuals may then function as aposematic models; thereby decreasing predatory attacks by vertebrate predators directed toward wasp kin and future offspring. This suite of defensive adaptations has enabled tarantula hawks to forage and behave with near impunity and to maximize their food and reproduction while having long adult lives virtually free from predation.