Numerous biologically active growth factors are secreted by the lacrimal gland and distributed via the tears over the ocular surface, where they affect cellular proliferation, migration, differentiation, and survival. The role of growth factors and their receptors in maintenance of tissue homeostasis and wound healing continues to be elucidated, and the effect of growth factor imbalances in ocular surface diseases is just beginning to be understood. For instance, in eyes with ocular surface diseases, including conjunctivitis, corneal erosion, keratitis, and corneal ulcers, epidermal growth factor release rates have been shown to be significantly lower than in normal eyes during reflex tearing. Future research into the mechanisms of dry eye disease will focus on reasons for decreased tear and growth factor production in the neuronal reflex loop or the acinar lacrimal gland cells. Animal models to test therapeutic approaches must be developed.