Two clinical cases are presented on patients with severe hypomagnesaemia induced by proton pump inhibitors. Laboratory data can help us to differentiate between hypomagnesaemia caused by intestinal loss of magnesium and the one produced by renal magnesium losses. Hypomagnesaemia associated with a prolonged use of proton pump inhibitors is an inadvertent adverse effect that can lead to severe clinical manifestations, therefore it is advisable to perform periodic monitoring of magnesium in the blood of patients who require prolonged treatment with proton pump inhibitors, especially in the concomitant use of antiarrhythmic or diuretic drugs, and in those patients with hypocalcaemia and/or hypokalaemia. The possibility of this and other adverse effects is one more reason to periodically evaluate long-term proton pump inhibitors treatment.