End-stage kidney disease (ESKD), defined as the need for dialysis, receipt of a transplant, or death from chronic kidney failure, generally affects fewer than 1% of the population. However ESKD is the end result of chronic kidney disease (CKD), a widely prevalent but often silent condition with elevated risks of cardiovascular morbidity and mortality and a range of metabolic complications. A recently devised classification of CKD has facilitated prevalence estimates that reveal an "iceberg" of CKD in the community, of which dialysis and transplant patients are the tip. Hypertension, smoking, hypercholesterolemia, and obesity, currently among the World Health Organization's (WHO's) top 10 global health risks, are strongly associated with CKD. The factors, together with increasing diabetes prevalence and an aging population, will result in significant global increases in CKD and ESKD patients. Treatments now available effectively reduce the rate of progression of CKD and the extent of comorbid conditions and complications. The challenges are (1) to intervene effectively to reduce the excess burden of cardiovascular morbidity and mortality associated with CKD, (2) to identify those at greatest risk for ESKD and intervene effectively to prevent progression of early CKD, and (3) to ultimately introduce cost-effective primary prevention to reduce the overall burden of CKD. The vast majority of the global CKD burden will be in developing countries, and policy responses must be both practical and sustainable in these settings.