It is still an urgent problem to regenerate and repair skin defects in clinic. Up to now, even though a lot of skin substitutes have been developed and realize the clinical application, most of them can only repair the structure of epidermis and simple dermis. The reconstructive skin tissue can＇t reconstruct the functions of normal skin, usually due to the lack of skin appendages, such as hair follicles, sweat glands and sebaceous glands. In this paper, from the aspects of seed cells, scaffold materials and its bioactivation, the skin substitutes with the ability of regenerating skin appendages, especially hair follicles were reviewed. Finally, some important challenges for the future studies in this field were discussed.