The focus of this review article is urea kinetic modeling based on the exploitation of concentration measurements in the spent dialysate stream. After a review of blood-based urea kinetic modeling, dialysate-based techniques are considered, beginning with dialysate collection techniques and their associated urea kinetic modeling equations. Partial dialysate collection methods and equations for the determination of protein catabolic rate based on a 7-day mass balance period are explored next. This is followed by a description of urea sensors and their application for dialysate-based modeling including the determination of protein catabolic rate, predialysis blood urea nitrogen (BUN), and KT/V. How the output of a urea sensor may allow the detection of significant changes in patient clearance during the course of dialysis is illustrated, as well as how double-pool urea kinetics may be accounted for in KT/V determination. Routine determination of patient lean body mass using creatinine kinetic modeling based on partial dialysate collection or a dialysate-based creatinine concentration sensor is demonstrated. Finally, the potential for complete automation of urea kinetic modeling in dialysis machines of the future is explored.