No longer an option of last resort, skin grafting has become a technique that is routinely and sometimes preferentially considered as skin replacement for burns, chronic ulcers, and skin defects after cutaneous surgical procedures. When selected as the best alternative for wound closure, autologous skin grafts are commonly considered the gold standard. Availability of autologous grafts is a major obstacle, however, and the search for a manufactured skin replacement has continued. In cases in which autologous grafts cannot be performed, skin substitutes have become an attractive alternative.