For over 50 years, there have been limited options for the management of hyperkalemia, especially among patients with chronic kidney disease (CKD), diabetic nephropathy, hypertension, and heart failure, who were receiving concomitant renin–angiotensin–aldosterone system (RAAS) inhibitor therapy. Hyperkalemia is a potential, life-threatening electrolyte abnormality that frequently challenges clinicians from maximizing the mortality benefit and organ-protective properties of RAAS inhibitors especially in CKD and heart failure populations. Patiromer is a novel nonabsorbed, cation-exchange polymer that binds and exchanges potassium for calcium, predominantly in the gastrointestinal tract. It has demonstrated potassium-lowering effects in normo- or hyperkalemic patients on concomitant RAAS inhibitors with heart failure, diabetic nephropathy, and CKD, in the PEARL-HF, AMETHYST-DN, and OPAL-HK studies, respectively. Across all studies, it appears to be generally effective and well tolerated, with adverse events predominantly gastrointestinal in nature. Additional investigational studies are needed to explore its use for an extended duration of treatment and in larger patient populations, as well as exploring drug–drug interactions. Overall, patiromer demonstrates a promising role in the chronic management of hyperkalemia that will allow optimization of RAAS inhibitor therapy, thus delaying progression of CKD and improving the mortality benefit in heart failure patients.