Drugs can interfere with the normal intake, elimination, regulation and total body distribution of electrolytes. These drug-induced abnormalities may be dramatic and life threatening, posing diagnostic and management problems to the physician who is not familiar with them. Serum potassium concentrations can be altered as potassium shifts between the tissue and plasma compartments secondary to drug actions. In addition, drugs have been shown to interfere with the normal physiological functioning of the kidney with respect to potassium homeostasis, as well as the renin-aldosterone axis. The regulation of serum sodium levels is integrally related to the regulation of total body water. Thus, drugs that alter the regulation of antidiuretic hormone secretion and its action on the kidney can result in large changes in serum sodium concentrations. Abnormal losses or intake of sodium related to drug use can also have profound effects in the plasma compartment. The normally fine regulation of serum calcium concentrations can be easily upset by pharmacological therapy at the level of parathyroid hormone secretion and action, bone metabolism or renal calcium excretion. Through awareness of these drug-induced changes in electrolytes and the mechanisms involved, subtle and often dangerous problems in clinical management can be handled rationally.