Reoperation for primary hyperparathyroidism (PHPT) remains a major challenge for both the patient and surgeons. Before considering reoperation, the surgeon must confirm the diagnosis of PHPT and assess patient risk factors. The goal of reoperative surgery is to excise the abnormal parathyroid gland(s) and limit exploration to help minimize the potential complications. At least two positive and concordant localizing studies should be available before reoperation, but the surgeon must keep in mind that the operative and histology reports from previous operation are the first localization techniques. A thorough knowledge of the anatomy and an understanding of the embryonic development of the parathyroid glands are also the keys to successful localization. According to the case history and the results of localization studies, the surgeon must clearly establish whether or not there is a suspicion of multiglandular disease (MGD). If the lesion sought is a solitary adenoma, an open-focused approach can be proposed. Conversely, if there is a confirmation or strong suspicion of MGD, revision of the transverse cervicotomy is recommended. In case of suspicion of local recurrence, an extensive local resection or en bloc resection may be indicated. Intraoperative QPTH assay is recommended to rule out MGD. In some cases, cryopreservation of parathyroid tissue and judicious use of parathyroid transplantation can be useful. With experienced parathyroid surgeons, the success rate of reoperations can be as high as 95%. It has been estimated that about 5% to 10% of initial operations for PHPT result in recurrent or persistent disease. It is too early to evaluate the real risk of persistent or recurrent disease following minimally invasive techniques, but any attempt to limit the extent of the primary procedure will be insignificant if the risk of persistent or recurrent disease is increased.