Severe ocular surface diseases are some of the most challenging entities currently facing ophthalmologists. The purpose of this review was to describe the recent advances, current developments, and future challenges related to ocular surface reconstruction from both the basic science and clinical aspects. To date, many candidate corneal epithelial stem-cell markers for tissue-engineered culture transplants have been proposed worldwide. Several groups have reported the long-term clinical results of cultivated epithelial transplantation for treating severe ocular surface disease. In an attempt to further develop the surgical procedures of ocular surface reconstruction, several groups recently reported using cells obtained from novel sources, surrounding cell substrates, and safer culture processes. As a result of the basic research and breakthroughs in the field of corneal regenerative medicine, great progress has been made in the basic understanding and development of new therapeutic tools.