During the past 50 years, a dramatic reduction in the mortality rate associated with cardiovascular disease has occurred in the US and other countries. Statistical modeling has revealed that approximately half of this reduction is the result of risk factor mitigation. The successful identification of such risk factors was pioneered and has continued with the Framingham Heart Study, which began in 1949 as a project of the US National Heart Institute (now part of the National Heart, Lung, and Blood Institute). Decreases in total cholesterol, blood pressure, smoking, and physical inactivity account for 24%, 20%, 12%, and 5% reductions in the mortality rate, respectively. Nephrology was designated as a recognized medical professional specialty a few years later. Hemodialysis was first performed in 1943. The US Medicare End-Stage Renal Disease (ESRD) Program was established in 1972. The number of patients in the program increased from 5,000 in the first year to more than 500,000 in recent years. Only recently have efforts for risk factor identification, early diagnosis, and prevention of chronic kidney disease (CKD) been undertaken. By applying the approach of the Framingham Heart Study to address CKD risk factors, we hope to mirror the success of cardiology; we aim to prevent progression to ESRD and to avoid the cardiovascular complications associated with CKD. In this paper, we present conceptual examples of risk factor modification for CKD, in the setting of this historical framework.