Although bilateral neck exploration is traditionally considered as the treatment of choice in patients with primary hyperparathyroidism (HPT), several surgical techniques of limited neck exploration have been proposed over the last 10 years in primary HPT patients with a high probability to be affected by a solitary parathyroid adenoma. The availability in recent years of highly sensitive and accurate preoperative imaging modalities, particularly the parathyroid scintigraphy with 99mTc-MIBI and high resolution neck ultrasonography, allowed to increase the rate of primary HPT patients as candidates to a selective parathyroidectomy. One of the most innovative techniques for limited surgery is the minimally invasive radio-guided parathyroidectomy that is based on the intraoperative detection of the parathyroid adenoma under the guidance of a gamma probe allowing the removal of the parathyroid adenoma through a small 2-cm skin incision. However, if a minimally invasive parathyroidectomy is taken into consideration, accurate preoperative imaging is mandatory not only to distinguish patients with a solitary parathyroid adenoma from those with multi-glandular disease but also to diagnose patients with concomitant thyroid nodule(s) that can cause false-positive results at radio-guided surgery. In the present study the most recent advances reached with preoperative localizing imaging of parathyroid adenomas are reviewed and the techniques proposed to perform a minimally invasive radio-guided surgery are discussed with particular regard to the therapeutic efficacy and cost-effectiveness analysis.