Uremia is characterized by gross contamination of body water with a wide spectrum of retained solutes normally excreted by the kidney. The rationale for dialysis therapy is that these retained solutes have concentration-dependent toxicity, which can be ameliorated through removal by dialysis. Apart from the well-established clinical consequences of abnormalities in fluid, electrolyte, acid base metabolism, and retained beta 2-microglobulin (beta 2 m), there is very little understanding of solute-specific uremic toxicity. Evidence is reviewed to demonstrate the following: (1) Many aspects of the uremic syndrome are controlled by adequate dialysis of low molecular weight solutes. (2) Urea can serve as a generic molecule to quantitate the fractional clearance of body water by dialysis (Kt/V) of retained low molecular weight solutes. (3) Urea has no concentration-dependent toxicity, and the generation rate of putative toxic low molecular weight solutes is not proportional to urea generation. The major clinical consequences and controversies stemming from these interrelationships are reviewed. Kinetic approaches to determine Kt/V dose equivalency between intermittent and continuous dialysis therapy are reviewed. We conclude that Kt/V can and will be generalized to describe the kinetics of other solutes such as beta2m as our knowledge of uremic toxicity grows, and hence, it is predicted that it will goeth and goeth and goeth.