Hypocalcemia (defined as total serum calcium lower than 8.5 mg/dl or as ionized serum calcium lower than 4.7 mg/dl) is a relatively common metabolic abnormality observed in hospitalized patients. Although it is associated with certain pharmacological agents such as bisphosphonates and cisplatin, hypocalcemia may occasionally develop in the course of treatment with drugs used in everyday clinical practice, including antiepileptics, aminoglycosides, and proton pump inhibitors. Hypocalcemia associated with drug treatment can be easily missed as a consequence of coexistence of multiple factors contributing to low serum calcium levels. Drug-related hypocalcemia is usually mild and asymptomatic but may be severe as well. Effective clinical management can be handled through awareness of this adverse effect induced by certain pharmaceutical compounds on serum calcium concentrations. Herein, we review pertinent clinical information on the incidence of hypocalcemia associated with specific drug treatment and discuss the underlying pathophysiological mechanisms.