Sex and the endocrine system exert a significant influence on the physiology and pathophysiology of the lacrimal gland. The purpose of this article is to briefly review the nature and magnitude of these interactions between sex, hormones and lacrimal tissue, and to address how they may relate to the pathogenesis of aqueous-deficient dry eye. Towards this end, this article has a 3-fold approach: first, to summarize the influence of androgens, estrogens, glucocorticoids, mineralocorticoids, retinoic acid, prolactin, alpha-melanocyte stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, growth hormone, thyroid-stimulating hormone, arginine vasopressin, oxytocin, thyroxine, parathyroid hormone, insulin, glucagon, melatonin, human chorionic gonadotropin and cholecystokinin on the structure and function of the lacrimal gland; second, to discuss the mechanism of action of each hormone on lacrimal tissue; and third, to discuss the clinical relevance of the endocrine-lacrimal gland interrelationship, with a particular focus on each hormone's role (i.e. if relevant) in the development of aqueous-tear deficiency.