Hyponatremia (defined as a serum sodium level < 134 mmol/L) is the most common electrolyte abnormality in hospitalized patients. Certain drugs (eg, diuretics, antidepressants, and antiepileptics) have been implicated as established causes of either asymptomatic or symptomatic hyponatremia. However, hyponatremia occasionally may develop in the course of treatment with drugs used in everyday clinical practice (eg, newer antihypertensive agents, antibiotics, and proton pump inhibitors). Physicians may not always give proper attention in time to undesirable drug-induced hyponatremia. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on serum sodium levels. Here, we review clinical information about the incidence of hyponatremia associated with specific drug treatment and discuss the underlying pathophysiologic mechanisms.