Current dialysis strategies only remove a fraction of the spectrum of putative uremic toxins largely because of these being bound to the protein. Further increases in membrane pore size with high-permeability dialyzers not only increase larger solute clearances, including free plasma light chains, peptides, and small proteins, but also result in albumin losses. Although removal of protein-bound toxins is increased with these high-permeability membranes, this is proportional to protein losses. Alternative strategies to increase removal of larger and protein-bound uremic toxins include alterations of the dialyzer surface characteristic to increase adsorption of toxins. Further work is required to clarify the toxicity of individual uremic retention products to determine whether groups or classes should be preferentially targeted. At some of the putative uremic toxins are derived from gastrointestinal bacterial metabolism, strategies aimed to change gastrointestinal bacterial flora may be an effective alternative strategy.