This lecture focuses on the complex of regulatory factors that maintain tear film homeostasis and on the main causes of tear film instability with qualitative or quantitative dry eye. Special attention is dedicated to the lacrimal functional unit including the cornea, with sensory nerve endings, the afferent and efferent innervation to stimulate lacrimal glands, meibomian glands and conjunctival goblet cells. Other important components for tear film stability are considered such as immune cells, microbiome, hormones, environmental factors and the eyelids’ function to protect the ocular surface and distribute the glandular secretion.