More than a century ago, Sir Henry Dale demonstrated that a component of the pituitary causes contractions of the mammalian uterus, hence his coining the term “oxytocic,” derived from the Greek for “quick birth,” for its activity. The discovery that a component of the pituitary causes milk secretion followed within a few years. By 1930, oxytocin was separated from vasopressin into pitocin and pitressin, respectively, at Parke Davis and made available for research. That a single peptide was responsible for these uterine and mammary actions was definitively confirmed upon the sequencing and synthesis of the peptide, 9 amino acids in length. Vincent du Vigneaud was awarded a Nobel Prize for this work. Oxytocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. Oxytocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. Uterine motility depends on the formation of the contractile protein actomyosin under the influence of the Ca2+- dependent phosphorylating enzyme myosin light-chain kinase. Oxytocin promotes contractions by increasing the intracellular Ca2+. Oxytocin has specific receptors in the myometrium and the receptor concentration increases greatly during pregnancy, reaching a maximum in early labor at term. The Oxytocin receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta. The high-affinity receptor state requires both Mg(2+) and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has been characterized by mutagenesis and molecular modeling and is different from the antagonist binding site. The function and physiological regulation of the Oxytocin system is strongly steroid dependent.