Using cystatin C, a novel serum marker of kidney function, several studies have shown that mild kidney dysfunction is associated with increased risk for cardiovascular disease and mortality. Studies have questioned, however, whether cystatin C is predominantly a measure of kidney function. This review summarizes the research literature on cystatin C. One longitudinal study in patients with diabetes found cystatin C to approximate glomerular filtration rate measures over 4 years much better than creatinine. Studies in several cohorts found cystatin C to be linearly associated with mortality, cardiovascular mortality, and heart failure risk, whereas creatinine predicted increased risk only in subjects with the worst kidney function. One study, however, found that increased age, male sex, increased height and weight, smoking, and higher C-reactive protein levels were associated with cystatin C after adjustment for creatinine clearance, which may suggest nonrenal influences on cystatin C concentrations. Cystatin C appears to capture the association of mild kidney dysfunction with increased risk for cardiovascular disease and death. Future research needs to evaluate whether cystatin C will have an important role in clinical medicine.