Herein we describe the case of a 64-year-old woman with hypoparathyroidism diagnosed at the age of 40, after an acute episode of tetany and seizures due to severe hypocalcemia. She was treated for more than 20 years with calcitriol and calcium supplementation but she presented with marked hypercalciuria and recently nephrolithiasis, although serum calcium was maintained at levels below normal range. Provided that any attempt to increase the recommended dose of calcitriol was leading to an exacerbation of hypercalciuria, we decided to enroll an alternative tool in the treatment strategy. In order to avoid further deterioration of renal function she was administered once-daily a subcutaneous (sc) injection of synthetic human parathyroid hormone (PTH 1-34) while doses of calcium and calcitriol were gradually decreased depending on the response of calcium metabolism in serum and urine samples taken periodically. Within two months of administration, PTH (1-34) significantly reduced the level of urine calcium excretion compared with calcitriol therapy and maintained serum calcium in the normal range. The relevant literature is reviewed in light of this alternative therapeutic approach in long-standing hypoparathyroidism, illustrating the potential benefits and the unresolved issues in parathyroid hormone replacement.