Reconstruction of skin defects is often a challenging effort due to the currently limited reconstructive options. In this sense, tissue engineering has emerged as a possible alternative to replace or repair diseased or damaged tissues from the patient's own cells. A substantial number of tissue-engineered skin substitutes (TESSs) have been conceived and evaluated in vitro and in vivo showing promising results in the preclinical stage. However, only a few constructs have been used in the clinic. The lack of standardization in evaluation methods employed may in part be responsible for this discrepancy. This review covers the most well-known and up-to-date methods for evaluating the optimization of new TESSs and orientative guidelines for the evaluation of TESSs are proposed.