Daily dietary potassium (K⁺) intake may be as large as the extracellular K⁺ pool. To avoid acute hyperkalemia, rapid removal of K⁺ from the extracellular space is essential. This is achieved by translocating K⁺ into cells and increasing urinary K⁺ excretion. Emerging data now indicate that the renal thiazide-sensitive NaCl cotransporter (NCC) is critically involved in this homeostatic kaliuretic response. This suggests that the early distal convoluted tubule (DCT) is a K⁺ sensor that can modify sodium (Na⁺) delivery to downstream segments to promote or limit K⁺ secretion. K⁺ sensing is mediated by the basolateral K⁺ channels Kir4.1/5.1, a capacity that the DCT likely shares with other nephron segments. Thus, next to K⁺-induced aldosterone secretion, K⁺ sensing by renal epithelial cells represents a second feedback mechanism to control K⁺ balance. NCC’s role in K⁺ homeostasis has both physiological and pathophysiological implications. During hypovolemia, NCC activation by the renin-angiotensin system stimulates Na⁺ reabsorption while preventing K⁺ secretion. Conversely, NCC inactivation by high dietary K⁺ intake maximizes kaliuresis and limits Na⁺ retention, despite high aldosterone levels. NCC activation by a low-K⁺ diet contributes to salt-sensitive hypertension. K⁺-induced natriuresis through NCC offers a novel explanation for the antihypertensive effects of a high-K⁺ diet. A possible role for K⁺ in chronic kidney disease is also emerging, as epidemiological data reveal associations between higher urinary K⁺ excretion and improved renal outcomes. This comprehensive review will embed these novel insights on NCC regulation into existing concepts of K⁺ homeostasis in health and disease.