The majority of patients with primary hyperparathyroidism have a single hyperfunctional gland. Based on this understanding, unilateral neck exploration was developed as an alternative to traditional bilateral surgery to minimize the extent of dissection and morbidity of parathyroid surgery. Successful unilateral parathyroid surgery requires that the surgeon understands the patient’s disease process and can assess the likelihood that the patient has primary hyperparathyroidism due to a single abnormal gland. Surgeons who perform unilateral exploration must also be able to accurately interpret preoperative imaging studies and recognize normal and abnormal glands, be well versed in intraoperative parathyroid hormone assay interpretation, and be prepared to convert to bilateral exploration when indicated.