Chronic kidney disease (CKD) is a global public health concern and a key determinant of poor health outcomes. While the burden of CKD is reasonably well defined in developed countries, increasing evidence indicates that the CKD burden may be even greater in developing countries. Diabetes, hypertension, and obesity are major contributors to the global burden of the disease and are important traditional CKD risk factors; however, nontraditional CKD risk factors such as nephrotoxin exposure, kidney stones, fetal and maternal factors, infections, environmental factors, and acute kidney injury are also increasingly being recognized as major threats to global kidney health. A broad approach to CKD prevention begins with the identification of CKD risk factors in the population, followed by the development of appropriate mitigation strategies. Effective prevention policies rely on an accurate understanding of the incidence and prevalence of CKD in a given setting, as well as the distribution and burden of risk factors. Populations or individuals at CKD risk must be screened and treated early to prevent the onset of and delay the progression of the kidney disease. Systematically collected data should be analyzed at country, province, and district levels to identify regional disparities and CKD hotspots and develop targeted prevention strategies. Race-ethnicity, genetics, sex, socioeconomic status, and geography are likely modifiers of CKD risk. A comprehensive, informed approach to prevention that takes into account all of these factors is therefore required to successfully tackle the global CKD epidemic.