The surgical management of patients with persistent or recurrent primary hyperparathyroidism is reviewed. The several factors allowing the surgeon to formulate a correct working diagnosis and to successfully remove all abnormal parathyroid tissue are individually discussed and recent results of re-operative parathyroid surgery are presented. In particular, direct surgical exploration based on aggressive pre-operative localization studies, the use of intra-operative ultrasound to facilitate intra-operative dissection, cryopreservation of excised parathyroid tissue with potential for delayed autograft to avoid permanent hypoparathyroidism, and the use of intra-operative monitoring of urinary cyclic adenosine monophosphate levels in patients with parathyroid hyperplasia in whom the surgeon is uncertain whether all abnormal parathyroid tissue has been removed, each contribute to a high rate of successful management (greater than 95%) for patients with the difficult problem of persistent or recurrent primary hyperparathyroidism.