The most important step in calcium homeostasis is the regulation of parathyroid hormone (PTH) secretion. The discovery and characterization of the calcium sensing receptor (CaR) of the parathyroid cell has led to a better understanding not only of the physiology of the parathyroid glands, but also of the development of hyperparathyroidism. Drugs acting on CaR can now be designed to treat hyperparathyroidism and osteoporosis.The workshop on primary hyperparathyroidism held at the National Institutes of Health in 2002 has recommended new guidelines for the treatment of asymptomatic hyperparathyroidism. Controversy still exists regarding the treatment of patients with nonclassical symptoms, such as weakness, fatigue and depression. Primary hyperparathyroidism as a risk factor for cardiovascular disease and mortality is also debated.Improved techniques for the preoperative localization of pathological parathyroid glands have led to a shift in surgical strategy: surgeons abandon the traditional bilateral neck exploration in favor of a more limited approach. This change of strategy has not been based on the results of prospective randomized studies and the long term results are not known.