Despite constant exposure to the environment the ocular surface rarely becomes infected. This immunity is conferred by a variety of physical and chemical mechanisms that cooperate to limit pathogen entry and kill or prevent the proliferation of microbes. This article provides an overview of the major mechanisms operating in the tears that bathe the ocular surface. These are primarily chemical and include antimicrobials such as lysozyme and secretory immunoglobulin A. The contributions from the corneal and conjunctival epithelial cells are also addressed and encompass the physical barrier created by the cells themselves and production of antimicrobial peptide such as defensins and LL-37.