The ocular surface usually looks quiet, presenting a general impression of biological inactivity. Yet, the ability of the cornea to maintain health while continually exposed to environmental insults, and in the relative absence of immune strategies afforded by other body sites, reflects its complexity. Because it is critical for transparency and, therefore, our survival, the fine structure of the cornea has likely provided the driving force for the evolution of what appears to be a truly remarkable system. While several molecules are now known to participate, we are only beginning to obtain the knowledge to fully explain the mechanisms involved in corneal resistance to infection. Full explanation will require a better understanding of the interplay between microbes and various components of the ocular surface, and of the critical factors determining health as the usual outcome. To understand infectious disease, we need to consider how the scenario changes in conditions associated with susceptibility. What we learn in the process could yield a wealth of potential therapies for a wide variety of diseases of the eye and of other sites.