The classic surgical approach to patients undergoing parathyroidectomy for primary or secondary hyperparathyroidism has experienced a dramatic shift owing to preoperative localization of the affected glands and/or the use of rapid intraoperative parathyroid hormone (RI-PTH) assays, allowing for minimally invasive surgical excisions. Institutional experience with 141 patients who underwent parathyroidectomy aided by the use of RI-PTH is reviewed. The orientation provided by the intraoperative assay is essential in guiding the surgeon in these minimally invasive procedures, it helps reveal the cases of primary hyperparathyroidism with involvement of more than 1 gland, and it replaces the need for performing frozen sections, except for cases of secondary hyperparathyroidism.