Clinical biochemists have long known the analytical and clinical limitations of creatinine and creatinine clearance measurement in the assessment of glomerular filtration rate (GFR). This background is reviewed in the article before assessing the utility of cystatin C, the most promising replacement biochemical marker yet identified. Cystatin C has been used in clinical research studies for more than 20 years and yet has been introduced into clinical practice in very few centres, firstly in Lund in Sweden and now Carshalton in the UK. Why is this? The review compares our ability to measure creatinine and cystatin C and their relative sensitivity and specificity for changes in GFR. Comparison is made of cystatin C with creatinine as screening tests for early renal dysfunction and for monitoring its progression where issues of reference ranges and within-individual variation are important. The superiority of cystatin C as a screening test is probably accepted but there are still concerns about non-renal influences upon its circulating concentration, particularly steroid therapy, insufficient data on the influence of malignancy and a general lack of prospective clinical studies confirming the prognostic significance of cystatin C.