The worldwide rise in the number of patients with chronic kidney disease (CKD) and consequent end-stage renal failure necessitating renal replacement therapy is threatening to reach epidemic proportions over the next decade, and only a small number of countries have robust economies able to meet the challenges posed. A change in global approach to CKD from treatment of end-stage renal disease (ESRD) to much more aggressive primary and secondary prevention is therefore imperative. In this Seminar, we examine the epidemiology of CKD worldwide, with emphasis on early detection and prevention, and the feasibility of methods for detection and primary prevention of CKD. We also review the risk factors and markers of progressive CKD. We explore current understanding of the mechanisms underlying renal scarring leading to ESRD to inform on current and future interventions as well as evidence relating to interventions to slow the progression of CKD. Finally, we make strategic recommendations based on future research to stem the worldwide growth of CKD. Consideration is given to health economics. A global and concerted approach to CKD must be adopted in both more and less developed countries to avoid a major catastrophe.