Stem cells are undifferentiated cells that can self-renew and give rise to differentiated progeny. All tissue renewal is done by stem cells or progenitor cells to replace differentiated cells that have died or been lost through normal turnover or injury. Corneal epithelium is maintained by corneal epithelial stem cells, which are adult stem cells which sustain a transparent corneal surface, and protect the cornea against environmental damages and microorganism and are located in the limbus in human, and hence are called limbal stem cells (LSCs). LSCs act as a barrier to prevent conjunctival epithelial from migrating to the corneal surface and the necessary microenvironment for their survival and to protect them from damages including ultraviolet (UV) radiation, trauma, and dryness. Limbal stem cell deficiency (LSCD) is classified into primary and secondary; Secondary corneal stem cell deficiency occurs as a result of external factors such as trauma, contact lens wear, systemic autoimmune diseases, ocular surgeries, limbal neoplasm and medications. LSC transplantation is necessary in total LSCD and is discussed in detail in the chapter.