Calcium channel blockers (CCBs) play a vital role in the management of hypertension. Peripheral edema is the most common side effect reported with CCB monotherapy, especially with high-dose dihydropyridine CCBs. CCB-related peripheral edema is a dose-limiting effect that is usually medically benign but can compromise patient adherence. CCB-related peripheral edema may cause considerable discomfort and patient concern. Patients presenting with peripheral edema should undergo assessment for drug and nondrug causes. Rather than lowering the CCB dose or switching to another monotherapy, combination therapy (e.g, CCB plus a renin-angiotensin-aldosterone system inhibitor) can enhance blood pressure control, generally with lower doses of individual agents, and lessen the risk of adverse events. As recommended by consensus guidelines, addition of a renin-angiotensin-aldosterone system inhibitor as part of combination therapy may accelerate the time to goal blood pressure as well as help alleviate peripheral edema in affected patients. Successful management of CCB-related peripheral edema with lifestyle changes and rational combination therapy is likely to improve blood pressure control and patient outcomes.