The majority of patients presenting with hyperparathyroidism have a single adenoma responsible for elevated parathyroid hormone levels. However, in about 10–15% of cases, two or more parathyroid glands are involved in the disease process. Thus, any surgical intervention must address all diseased glands in order to provide benefit to the patient. While multiglandular disease is commonly sporadic, multiple other factors may lead to gland enlargement, including drugs such as lithium, renal disease, and genetic disorders such as multiple endocrine neoplasia; in these instances, significantly more investigation and/or treatment is required than in those patients with sporadic disease. Thus, the clinician must carry a heightened level of suspicion for other causes of disease when multiglandular disease is recognized.