Millions of workers around the world are exposed to high temperatures, intense physical activity, and lax labor practices that do not allow for sufficient rehydration breaks. The extent and consequences of heat exposure in different occupational settings, countries, and cultural contexts is not well studied. We conducted an in-depth review to examine the known effects of occupational heat stress on the kidney. We also examined methods of heat-stress assessment, strategies for prevention and mitigation, and the economic consequences of occupational heat stress. Our descriptive review summarizes emerging evidence that extreme occupational heat stress combined with chronic dehydration may contribute to the development of CKD and ultimately kidney failure. Rising global temperatures, coupled with decreasing access to clean drinking water, may exacerbate the effects of heat exposure in both outdoor and indoor workers who are exposed to chronic heat stress and recurrent dehydration. These changes create an urgent need for health researchers and industry to identify work practices that contribute to heat-stress nephropathy, and to test targeted, robust prevention and mitigation strategies. Preventing occupational heat stress presents a great challenge for a concerted multidisciplinary effort from employers, health authorities, engineers, researchers, and governments.