Studies on the population genetics, phylogenetic relationships, systematics and evolution of arthropods that inhabit necrotic tissue of cacti in the Sonoran Desert of North America are reviewed. These studies have focused upon several species of insects (orders Diptera and Coleoptera) and arachnids (order Pseudoscorpiones). For most taxa studied, little genetic structure and high dispersal ability are found in populations inhabiting the mainland and Baja California peninsula regions of the Sonoran Desert, consistent with the availability of the rotting cactus microhabitat which is patchily distributed and ephemeral. There is evidence, however, that the Gulf of California, which bisects the Sonoran Desert, has played a role in limiting gene flow and promoting speciation in several taxa, including histerid beetles, whereas other taxa, especially Drosophila nigrospiracula and D. mettleri, apparently are able to freely cross the Gulf, probably by taking advantage of the Midriff Islands in the northern Gulf as dispersal “stepping stones”. Genetic evidence has also been found for historical population expansions dating to the Pleistocene and late Pliocene in several taxa. Overall, these studies have provided important insights into how arthropods with different life history traits, but generally restricted to a necrotic cactus microhabitat, have evolved in an environmentally harsh and tectonically active region. In addition, they suggest some taxa for further, and more detailed, hypothesis driven studies of speciation.