The ocular surface, in a strict sense, consists of the cornea and its major support tissue, the conjunctiva. In a wider anatomical, embryological, and also functional sense, the ocular mucosal adnexa (i.e. the lacrimal gland and the lacrimal drainage system) also belong to the ocular surface. This definition includes the source and the eventual drainage of the tears that are of utmost importance to ocular surface integrity. The ocular surface is directly exposed to the external environment, and therefore is endangered by a multitude of antigens and pathogenic microorganisms. As a mucosa, it is protected by the mucosal immune system that uses innate and adaptive effector mechanisms present in the tissue and tear film. Immune protection has two partly opposing tasks: the destruction of invading pathogens is counterbalanced by the limitation of inflammatory events that could be deleterious to the subtle structure of the eye. The immune system of the ocular surface forms an eye-associated lymphoid tissue (EALT) that is recognized as a new component of the mucosal immune system. The latter consists of the mucosa-associated lymphoid tissues in different organs of the body. Mucosa- and hence eye-associated lymphoid tissues have certain characteristics that discriminate them from the central immune system. The mechanisms applied are immunological ignorance, tolerance, or an immunosuppressive local microenvironment, all of which prefer non-reactivity and anti-inflammatory immunological responses. The interaction of these mechanisms results in immune privilege of the ocular surface. During eye closure, the ocular surface appears to have different requirements that make an innate pro-inflammatory environment more attractive for immune defense. The structural and functional components that contribute to this special immune regulation will be the focus of this chapter.