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Over the last decade, the relevance of the pituitary-bone axis has been recognized.  Oxytocin (OXT), arginine vasopressin (AVP), growth hormone (GH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH) and prolactin have a dominant action on the skeleton as demonstrated by the fact that genetically modified mice lacking their ligands or receptors exhibit a skeletal phenotype, although the primary target organs remain unaltered.  Unraveling these new mechanisms of action of the pituitary hormones has paved the way for new therapeutic opportunities in the treatment of osteoporosis.  Here, we summarize the action and interaction of OXT and AVP, closely related small peptides that modulate reciprocal secretion and receptor expression on bone cells, in the physiologic context of the skeletal homeostasis.