This Practice Point commentary discusses a recent paper by Menon et al. that described the natural history of a cohort of nondiabetic patients with stage 2-4 chronic kidney disease (CKD) who had been recruited from nephrology practices and screened for entry into the Modification of Diet in Renal Disease (MDRD) trial. Kidney failure was the most common outcome during long-term follow-up among these patients and there was a low competing risk of death, findings in contrast to observations in other cohorts of patients with CKD. Patients with lower glomerular filtration rate and greater proteinuria at baseline were at increased risk for both kidney failure and death, but kidney failure remained more likely than death in all glomerular filtration rate subgroups. These results emphasize the heterogeneity of the CKD population. Nephrologists should not rely on CKD staging alone to direct management of or risk-stratify patients with CKD, but should also consider the etiology and rate of progression of kidney disease, patient age and cardiovascular disease risk factors.