Ancient literature contained suggestions of references to people whom we might now speculate suffered from chronic renal failure; however, the first glimmerings of an understanding of the subject arose out of the clinico-pathological correlations that a number of 18th and 19th century observers drew. The concurrent studies by chemists of circulating and urinary levels of urea, creatinine, urate, phosphate, potassium, sodium and hydrogen ions expanded those correlations to a pathophysiological domain, especially in the late 19th and early 20th centuries. With the subsequent development of ideas about circulating hormones and the development of techniques for their measurement during the 20th century, the contemporary idea of chronic renal failure developed. The development of methods for quantifying tests of renal function enhanced that undertaking. Then, in the latter half of the 20th century, the development of effective dialytic techniques for the treatment of patients who suffer from chronic renal failure brought a renewed focus upon the mechanisms involved and problems posed by existing ideas. Nevertheless, the continuing high morbidity and mortality of patients who require such treatment suggest that existing ideas remain quite imperfect.