Prior to the availability of hemodialysis, dietary protein restriction played a large part in the treatment of uremia. This therapy was based on observations that uremic symptoms increased with high protein intake. Early investigators thus presumed that “uremic toxins” were derived from the breakdown of dietary protein; its restriction improved uremic symptoms but caused malnutrition. After the availability of hemodialysis, protein restriction was no longer recommended. Studies in healthy subjects have shown that an intake of 0.6–0.8 g/kg/day is adequate to prevent protein malnutrition. Guidelines for hemodialysis patients, however, currently recommend higher protein intakes of 1.2 g/kg/day. A downside to higher intake may be increased production of protein-derived uremic solutes that caused the symptoms observed by early investigators. Some of these solutes are produced by colon microbes acting on protein which escapes digestion in the small intestine. Increasing dietary fiber may reduce the production of colon-derived solutes in hemodialysis patients without adverse effects of protein restriction. Fiber comprises carbohydrates and related substances that are resistant to digestion in the small intestine. Upon delivery to the colon, fiber is broken down to short chain fatty acids, providing energy to both the microbes and the host. With an increased energy supply, the microbes can incorporate dietary protein for growth rather than breaking them down to uremic solutes. Increasing fiber intake in hemodialysis patients has been shown to reduce the plasma levels of selected colon-derived solutes. Further studies are needed to test whether this provides clinical benefit.