Parathyroid hormone (PTH) plays a critical role in mineral ion homeostasis, particularly in bone and kidney. A related peptide, parathyroid hormone-related peptide (PTHrP), plays an important role in skeletal development. Both peptides exert their biological actions by binding to a class B GPCR, PTH1, that signals primarily by activation of adenylate cyclase. Mutations in PTH1 have been identified as the cause of Jansen"s metaphyseal chondrodysplasia, Blomstrand"s chondrodysplasia, and enchondromatosis. Intermittent treatment with PTH has important clinical utility in building bone mass in patients with osteoporosis.