Eight methods to estimate urea distribution volume and generation rate from blood urea samples measured in dialysis patients are reviewed. An analytical solution has been provided for a double-pool variable volume kinetic model to allow for faster and more accurate simulation and identification. The reliable parameter estimates provided by the double-pool kinetic model starting from seven samples, were assumed as references for the estimates obtained by the remaining methods. These include three kinetic models and four methods based on urea mass-balance. In particular, the estimation techniques differ in the number of compartments where urea is assumed distributed (double- and single-pool) or in the number of blood urea samples. Among the methods based on mass-balance, two techniques neglecting the weight loss or the urea generation during dialysis, were also analysed. The results obtained during hemofiltration sessions using three samples, usually available in clinical practice at the beginning and at the end of dialysis, demonstrate that a new method based on double-pool kinetics provides, on average, the most reliable estimates. Moreover, methods belonging to a single pool view and including both weight loss and urea generation during dialysis seem to underestimate by 1 divided by 2 liters the urea distribution volume. However, neglecting the weight loss or the urea generation can overcompensate this error, resulting in a significant overestimation of the distribution volume. Finally, it has been experimentally proved that the single-pool kinetic methods overestimate the urea production rate, while techniques based on mass balance provide more reliable values.