Recurrent or persistent primary hyperparathyroidism is characterized by elevated calcium and PTH levels after prior parathyroid surgery. Reoperative parathyroid surgery requires a systematic approach as the chance of cure is reduced and the risk of complications is increased compared to primary surgery. Prior to embarking on reoperative parathyroid surgery, the surgeon should review the prior and current biochemical workup to confirm the diagnosis and review the prior operative notes, pathology, imaging, and intraoperative PTH results in an attempt to understand the extent of original surgery and potential cause for failure. An understanding of parathyroid embryology and anatomy, utilization of intraoperative PTH monitoring, preoperative imaging, radiopharmaceutical guidance, jugular venous sampling, and RLN monitoring are all important considerations and adjuncts which may be helpful in reoperative parathyroid surgery. It is incumbent on the surgeon to optimize chances of success utilizing available localization techniques and by exercising careful, calculated clinical judgment. This chapter addresses the complexities of reoperative parathyroid surgery in detail.