Total-body potassium (K) content and appropriate distribution of K across the cell membrane is vitally important for normal cellular function. Total-body K content is determined by changes in excretion of K by the kidneys in response to intake levels. Under normal conditions, insulin and β-adrenergic tone also make important contributions in maintaining internal distribution of K. However, despite these homeostatic pathways, disorders of altered K homeostasis are common. Appreciating the pathophysiology and regulatory influences that determine the internal distribution and external balance of K is critical in designing effective treatments to restore K homeostasis. We provide an up-to-date review of the regulatory aspects of normal K physiology as a preface to highlighting common disorders in K homeostasis and their treatment. This review of K homeostasis is designed as a resource for clinicians and a tool for educators who are teaching trainees to understand the pivotal factors involved in K balance.