Sodium polystyrene sulfonate (SPS), FDA-approved more than 60 years ago for treating hyperkalemia, is an ion exchange resin that works by exchanging sodium for potassium in the colon. Though widely used in clinical practice, SPS use is not supported by well-designed clinical trials. In 2009, the FDA issued a warning that SPS was associated with colonic necrosis and other serious gastrointestinal adverse reactions. This article reviews the pros and cons of SPS therapy.