The hormonal status and in particular sex steroids play a role in the ocular surface homeostasis and function, during the whole life and in both sexes, accomplished by estrogenic and androgenic receptors located on corneal and conjunctival epithelia and Meibomian gland. The ocular surface is an integrated unit and any dysfunction results in a scarce or unstable preocular tear film which produces dry eye, a chronic inflammatory condition with increasing incidence as people get older but always more frequent among females. In post-menopausal women endocrine changes join the aging effects in the pathogenesis of dry eye, but still it remains controversial whether estrogen or androgen deficiency or their imbalance impair ocular surface function. Another questionable issue concerns the efficacy of hormonal replacement therapy in the amelioration of dry eye symptoms and recovery of tear function, since the scientific literature stands in between a therapeutic or a promoting effect of eye dryness. Therapy of dry eye is usually based upon topical administration of tear substitutes; estrogen or androgen-based eye drops represents a promising innovative treatment based upon important scientific rationale.