Open AccessThe human tear film is a multi-layered and chemically complex structure, which performs numerous functions relating to the health of the corneal surface. One of the core functions of the tear film is to protect the eye against invasion by pathogens. Thus its middle layer, the ‘core aqueous stratum’, harbours a myriad of immunologicaland antimicrobial proteins. In this review we discuss the most abundant of these proteins (immunoglobulins, toll-like receptors, cytokines, lactoferrin, lysozyme, lipocalins, surfactant protein-Aand -D and defensins). In order to illustrate how the levels of immunological/antimicrobial proteins in tears change in response to eye disease, we review literature in which levels of these proteins have been measured in tears of patients with dry eye disease (DED) and keratoconus (KC). Finally, we report results of a preliminary study to measure the concentration of secretory immunoglobulin A (sIgA) in the tears of DED and KC patients. The study showed a significant decrease of sIgA levels in DED compared to control. Further analysis must be done to determine whether or not DED and KC may be associated with differential expression of immune proteins. (S Afr Optom 2012 71(3) 123-132)