Until recently, the ocular surface was thought by many to be sterile and devoid of living microbes. It is now becoming clear that this may not be the case. In this lecture, St. Leger will describe how he and colleagues discovered an immunologically relevant commensal bacterium of the ocular surface. St. Leger will describe how the immune response directed against this bacterium induces the formation of protective immunity, which helps the eye prevent other more serious bacterial and fungal infections. St. Leger will describe his lab’s more recent pursuits of showing how this commensal/host immune relationship affects disease associated with ocular herpes simplex virus type 1 (HSV-1) infection, and he will show more recent data from a collaboration with the UPMC Eye Center,where he and colleagues profile the ocular mucosal immune response from humans with and without ocular surface disease. Finally, St. Leger will show how researchers may be able to manipulate this relationship in humans to better treat ocular diseases, how microbes at the ocular surface affect local immunity, and how he and colleagues may be able to modulate this response in the future to alleviate ocular diseases.