Parathyroid hormone-related protein (PTHrP) is the factor responsible for the syndrome of humoral hypercalcemia of malignancy. PTHrP is produced by a multitude of normal as well as malignant cells, and exerts both classic parathyroid hormone (PTH)-like and PTH-unlike effects. The molecular cloning of the PTHrP gene, and the subsequent recognition of its widespread expression in normal tissues under normal physiologic conditions, has prompted intense inquiry into its biologic function. PTHrP appears to act in an autocrine or paracrine fashion in (a) normal embryogenesis and neonatal development, (b) cellular growth and differentiation, (c) reproduction and lactation, (d) epithelial calcium transport, and (e) smooth muscle relaxation. These five key emerging physiologic roles of PTHrP are the focus of this review.