The cornea is a unique tissue due to its transparency and avascularity. The cornea consists of three distinct cell layers: the outer epithelium, the central stroma, and the inner endothelium. The corneal epithelium plays a role in the innate immune response by sensing the presence of pathogens and providing signals to activate the corneal defense system. Corneal epithelial cells also express a high level of aldehyde dehydrogenase to protect them against UV- and 4-hydroxynonenal-induced cellular damage. The renewal of corneal epithelium depends on a a host of cytokines, including epidermal growth factor; which activates their cognate receptors in the deeper layers of the epithelium. Human corneal epithelial cells can be an alternative to animal testing in toxicology studies. They are also useful tools to understand the highly integrated balance between corneal epithelial proliferation, differentiation, and cell death.