Chemical injuries of the eye may produce extensive damage to the ocular surface epithelium, cornea, and anterior segment, resulting in permanent unilateral or bilateral visual impairment. Pathophysiological events which may influence the final visual prognosis and which are amenable to therapeutic modulation include 1) ocular surface injury, repair, and differentiation, 2) corneal stromal matrix injury, repair and/or ulceration, and 3) corneal and stromal inflammation. Immediately following chemical injury, it is important to estimate and clinically grade the severity of limbal stem cell injury (by assessing the degree of limbal, conjunctival, and scleral ischemia and necrosis) and intraocular penetration of the noxious agent (by assessing clarity of the corneal stroma and anterior segment abnormalities). Immediate therapy is directed toward prompt irrigation and removal of any remaining reservoir of chemical contact with the eye. Initial medical therapy is directed promoting re-epithelialization and transdifferentiation of the ocular surface, augmenting corneal repair by supporting keratocyte collagen production and minimizing ulceration related to collagenase activity, and controlling inflammation. Early surgical therapy if indicated, is directed toward removal of necrotic corneal epithelium and conjunctiva, prompt re-establishment of an adequate limbal vascularity, and re-establishment of limbal stem cell population early in the clinical course, if sufficient evidence exists of complete limbal stem cell loss. Re-establishment of limbal stem cells by limbal autograft or allograft transplantation, or by transfer in conjunction with large diameter penetrating keratoplasty, may facilitate development of an intact, phenotypically correct corneal epithelium. Limbal stem cell transplantation may prevent the development of fibrovascular pannus or sterile corneal corneal ulceration, simplify visual rehabilitation, and improve the visual prognosis. Advances in ocular surface transplantation techniques which allow late attempts at visual rehabilitation of a scarred and vascularized cornea include limbal stem cell transplantation for incomplete transdifferentiation and persistent corneal epithelial dysfunction, and conjunctival and/or mucosal membrane transplantation for ocular surface mechanical dysfunction. Rehabilitation of the ocular surface may be followed, if necessary, by standard penetrating keratoplasty if all aspects of ocular surface rehabilitation are complete, or by large diameter penetrating keratoplasty if successful limbal stem cell transplantation cannot be achieved but other ocular surface rehabilitation is complete.