The deserts and arid regions of North, Central, and South America are unique in the world because of the frequent dependence of their often-dominant plants (Cactaceae, Agavaceae) on nectar-feeding bats (Phyllostomidae: Glossophaginae and Lonchophyllinae) for pollination. In no other deserts have such specialized nectar bat-flowering plant mutualisms evolved. Three lineages of morphologically specialized phyllostomid nectar bats (Leptonycteris, Choeronycteris, and Platalina) are involved in this mutualism: the former two genera occur in Mexico, southwestern United States, and, in the case of Leptonycteris, northern South America whereas the latter genus occurs in the central Andes of South America. In this paper we describe the importance of Leptonycteris and Choeronycteris as pollinators of columnar cacti and paniculate agaves in North American deserts, discuss the evolutionary history of these interactions, and briefly compare these interactions with those in other Neotropical arid regions. We point out that because of their wide-ranging foraging and migratory behavior Leptonycteris bats are critical for maintaining genetic connectivity among populations of their food plants. Recent phylogenetic studies indicate that nectar bats have also been an important factor behind the high diversification rates of columnar cacti and paniculate agaves in the past 10 million years. Because of the unique ecological and evolutionary importance of these bats, their conservation should be a high priority.