The prevalence of chronic renal disease is increasing dramatically in industrialized nations. Recent surveys in Europe and the US show that about 10% of the total population are affected. Patients with end stage disease, necessitating dialysis or transplantation, are only the tip of the iceberg. Even with treatment these subjects suffer from a massive reduction in quality and quantity of life despite consuming a large proportion of healthcare expenditures. As quite effective treatment strategies are available to prevent progression there is a pressing clinical need for early detection, differential diagnosis and assessment of the individual prognosis of renal disease. The current gold standard is the measurement of serum creatinine; despite the fact this method has some major limitations. These can be partially overcome by the use of newer markers like Cystatin C. However, a major problem using this approach is the fact that serum creatinine and Cystatin C are markers of renal excretory function only and hence no differential diagnosis can be derived from them. Furthermore a single measurement is not sufficient to estimate the prognosis of an individual patient, especially in the early stages of the disease, making tailored treatment difficult. In this review we will summarize our current knowledge about the markers in use today and also provide information on new, potentially superior markers, which would enable a much more complete non-invasive assessment of a growing patient population.