Magnesium is the second intracellular cation and the fourth most abundant mineral in the body. Low levels of magnesium have been associated with insulin resistance and type-2 diabetes mellitus, asthma, osteoporosis and chronic kidney disease (CKD). The use of proton pump inhibitors (PPIs) represents the most common cause of hypomagnesemia. The risk of hypomagnesemia, and consequently worsening of the renal function, is increased when diuretics are added to therapy in subjects treated with PPIs. Interestingly, diuretics and PPIs are two of the most used drugs in subjects with CKD. In this review, we described the mechanisms at the basis of the hypomagnesemia and the effect of this electrolyte disturbance in subjects with CKD.