The lacrimal gland is the primary source for the aqueous portion of the tear film. This portion contains water, electrolytes and proteins, which are necessary for the health and maintenance of the cells of the ocular surface. Afferent sensory nerves in the cornea and conjunctiva stimulate efferent parasympathetic and sympathetic nerves in the lacrimal gland. Cholinergic agonists, released from parasympathetic nevres, and norepinephrine, released from sympathetic nerves, are major stimuli of lacrimal gland secretion. These neurotransmitters activate distinct, but overlapping signal transduction pathways leading to lacrimal gland secretion. Other stimuli of lacrimal gland secretion are the EGF family of growth factors. In addition to stimulation of secretion, these growth factors can interact with the cells of the lacrimal gland themselves or with the cells of the ocular surface depending upon the location from which these growth factors are released. This review will focus on the effects of the EGF family of growth factors on the lacrimal gland and their interactions with the pathways stimulated by the neurotransmitters released from nerves.