Background: Colon microbes produce a large number of organic compounds that are foreign to mammalian cell metabolism. Summary: Some of the compounds made by microbes are absorbed in the colon and then normally excreted by the kidneys. Accumulation of these compounds in the plasma as uremic solutes may contribute to illness in patients whose kidneys have failed. Mass spectrometry is expanding our knowledge of the chemical identity of the colon-derived uremic solutes, and DNA sequencing technologies are providing new knowledge of the microbes and metabolic pathways by which they are made. Because they are made in an isolated compartment by microbes, their production may prove simpler to suppress than the production of other uremic solutes. Key Messages: To the extent that they are toxic, suppressing their production could improve the health of renal failure patients without the need for more intensive or prolonged dialysis.