Because of the increasing concerns about climate change and deadly heatwaves in the past, the health effects of hot weather are fast becoming a global public health challenge for the 21st century. Some cities across the world have introduced public health protection measures, with the timely provision of appropriate home-based prevention advice to the general public being the most crucial point of intervention. In this Review, we report current epidemiological and physiological evidence about the range of health effects associated with hot weather, and draw attention to the interplay between climate factors, human susceptibility, and adaptation measures that contribute to heat burdens. We focus on the evidence base for the most commonly provided heat-protection advice, and make recommendations about the optimum clinical and public health practice that are expected to reduce health problems associated with current and future hot weather.