To live and thrive in arid environments place enormous evolutionary pressure on processes of water conservation. These are epitomized by the numerous adaptations manifested in those mammals specialized to limited water access, such as camels. At the level of the kidney, camels produce low volumes of highly concentrated urine, more so when water is scarce, to conserve body water. Two hormones, arginine vasopressin (AVP) and oxytocin (OXT), both produced in the supraoptic nucleus (SON), the core hypothalamic osmoregulatory control centre, are vital for this adaptive process. This chapter reviews what we know about the mechanisms that enable water-stressed mammals to cope with osmotic challenge. We describe the evolution of AVP-like molecules from invertebrates to mammals, the roles of AVP and OXT in osmoregulation, the structural/functional adaptations of the hypothalamus-kidney axis associated with AVP and the specific water conservation strategies employed by camels. Comparative studies on the molecular sequences of the AVP and OXT genes in mammals have revealed conserved and divergent elements across species. The homogeneity of these neuropeptides could be affected by their evolutionary relationships and the environmental stressors (such as aridity) that may have shaped their genetic structures. This chapter highlights the common elements between camels and other species that could be key factors of water homeostasis, as well as elements that appear to be unique to the camels that might be essential for adaptations necessary for life in the desert. For future studies, the identification of genetic variations associated with osmoregulation will provide insights for evaluating the possibility of evolutionary rescue of species currently challenged by increased desertification, especially the extremely endangered wild camels.