Clinical or subclinical hyperparathyroidism is one of the most common endocrine disorders. Excessive secretion of parathyroid hormone is most frequently caused by an adenoma of >or=1 parathyroid gland. Unsuccessful surgery with persistent hyperparathyroidism, due to inadequate preoperative or intraoperative localization, may be observed in about 10% of patients. The conventional surgical approach is bilateral neck exploration, whereas minimally invasive parathyroidectomy (MIP) has been made possible by the introduction of (99m)Tc-sestamibi scintigraphy for preoperative localization of parathyroid adenomas. In MIP, the incision is small, dissection is minimal, postoperative pain is less, and hospital stay is shorter. Localization imaging techniques include ultrasonography, CT, MRI, and scintigraphy. Parathyroid scintigraphy with (99m)Tc-sestamibi is based on longer retention of the tracer in parathyroid than in thyroid tissue. Because of the frequent association of parathyroid adenomas with nodular goiter, the optimal imaging combination is (99m)Tc-sestamibi scintigraphy and ultrasonography. Different protocols are used for (99m)Tc-sestamibi parathyroid scintigraphy, depending on the institutional logistics and experience (classical dual-phase scintigraphy, various subtraction techniques in combination with radioiodine or (99m)Tc-pertechnetate). MIP is greatly aided by intraoperative guidance with a gamma-probe, based on in vivo radioactivity counting after injection of (99m)Tc-sestamibi. Different protocols used for gamma-probe-guided MIP are based on different timing and doses of tracer injected. Gamma-probe-guided MIP is a very attractive surgical approach to treat patients with primary hyperparathyroidism due to a solitary parathyroid adenoma. The procedure is technically easy, safe, with a low morbidity rate, and has better cosmetic results and lower overall cost than conventional bilateral neck exploration. Specific guidelines should be followed when selecting patients for gamma-probe-guided MIP.