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Skin is an attractive model organ to test novel concepts of regenerative medicine, with a particular emphasis on skin regeneration for acute or chronic wounds. Chronic wounds present a worldwide growing health and economic problem because of a steadily increasing number of patients, high morbidity and risk of amputations, unsatisfactory results of existing therapies and heavy socioeconomic burden. Tissue-engineered skin substitutes represent an innovative therapeutical option for the treatment of acute and chronic skin wounds. Bioengineered skin replacements are not only supposed to substitute the major physiological functions by providing a rapid and reliable cover of the defect but also should be easily applicable under routine use conditions and reduce pain and discomfort for the patient. Furthermore, they should elicit the regeneration process from the wound bed without causing inflammation or rejection. Skin substitutes should be available immediately, and be non-toxic nor immunogenic. From an aesthetic point of view, skin substitutes should be durable, elastic, with minimized scar formation, and pigmentation should resemble natural skin.