Serious hyperkalemia is common in patients with end-stage renal disease (ESRD) and accounts for considerable morbidity and death. Mechanisms of extrarenal disposal of potassium (gastrointestinal excretion and cellular uptake) play a crucial role in the defense against hyperkalemia in this population. In this article we review extrarenal potassium homeostasis and its alteration in patients with ESRD. We pay particular attention to the factors that influence the movement of potassium across cell membranes. With that background we discuss the emergency treatment of hyperkalemia in patients with ESRD. We conclude with a review of strategies to reduce the risk of hyperkalemia in this population of patients.