The adequacy of hemodialysis is now assessed by measuring the removal of a single solute, urea. The urea clearance provided by current dialysis methods is a large fraction of the blood flow through the dialyzer, and, therefore, cannot be increased much further. However, other solutes, which are less effectively cleared than urea, may contribute more to the residual uremic illness suffered by patients on hemodialysis. Here, we review a variety of methods that could be used to increase the clearance of such nonurea solutes. New clinical studies will be required to test the extent to which increasing solute clearances improves patients' health.