The innate immune system of the eye is similar to other mucosal surfaces. The first tier is passive and consists of several anatomic, physical and chemical barriers that collaborate to prevent infection without inducing inflammation. The second tier is active and consists of cellular and secretory components that together cause acute inflammation aimed at eradicating the pathogen. The defenses confront a considerable challenge and infections become a significant cause of morbidity. The essential function of the ocular surface, epithelia and tears in the first place is to create a great barrier that prevents microbial attachment, killing or at least stopping proliferation of constantly attacking organisms, and provide a detection system that in the case of disruption of the primary innate defenses, can activate the adaptive immunity to provide further help to eliminate offending infectious elements. In this paper we describe and discuss a potential impact and clinical implications of extended contact lens wear on the immunity of the ocular surface emphasizing in particular the influence of pathogens like Pseudomonas aeruginosa, Fusarium or Acanthamoeba.