Drylands range across more than half of the global terrestrial area and harbour about a quarter of continental vertebrate species, many of them endemic. However, this fauna is being increasingly threatened, in particular the one that inhabits deserts, one of the last biomes on earth. This work tracks the most relevant global change drivers acting on drylands, especially in deserts and arid regions, the conservation actions being developed, and the research needs for vertebrate conservation, following IUCN standardised classification schemes. Using the Sahara-Sahel wetlands as case study, it is provided a detailed examination of these aspects to support regional biodiversity conservation and human welfare. Deserts and arid regions are threatened by the synergistic effects of increasing development of urban areas, agriculture, energy production, mining, transportation and service corridors, resulting in pollution, invasive species, human intrusions and disturbance, biological resource overuse and in general, natural system modifications. In addition, climate change together with social underdevelopment of many desert-range countries places the mitigation of threat factors in a large and complex web of global-local societal challenges. Conservation actions targeting land/water and species protection and management, as well as education, awareness, capacity building, and legislation measures to increase livelihood development, are being developed. Additional research efforts are need to enhance biodiversity conservation planning, monitoring biodiversity and land-degradation status (based on Essential Biodiversity Variables), and quantification of socioeconomic factors associated with sustainable use of natural resources and human development. Sahara-Sahel wetlands are important life-support systems for both humans and vertebrates, the last vulnerable to listed global threats. They offer framework scenario to revert current environmental and societal challenges in deserts. Long-term conservation of desert vertebrate biodiversity requires appropriate policy instruments to promote sustainable use of natural resources. Raising environmental alertness within local communities of uniqueness of desert biodiversity is needed to promote policy change.