Despite constant exposure to the external environment, the ocular surface rarely succumbs to infection. In general, such infection occurs only in the case of mechanical disruption of the epithelial barrier as a result of contact lens wear or injury. Prolonged or overnight contact lens wear resulting in corneal stress may contribute to increased corneal susceptibility to infections and inflammation. Infection can affect both the cornea (infectious keratitis) and conjunctiva (infectious conjunctivitis), but it is the most serious when the cornea is involved because of its role in providing the majority of the refracting power of the eye and in consequence this may lead to loss of visual acuity or even blindness. In this paper we describe a potential effect of prolonged contact lens wear on the pathophysiology of the ocular surface in its immunological and molecular aspects.