The skin acts as a barrier to exogenous substances, pathogens, and trauma. Skin defects caused by burns, venous ulcer, diabetic ulcer, or acute injury occasionally induce life-threatening situations. Tissue engineering provides an alternative for autologous or allogeneic tissue transplantation, which is required because of donor site limitations and the risks of transmitting infection. Currently, skin substitutes are made of only extracellular matrix, mainly cells, or combination of cells and matrices. New biotechnological approaches have led to the development of the skin equivalent, the closest match yet to native human skin in terms of histological and functional properties. This review article focuses upon the development of the in vitro and in vivo epidermis and dermis and their clinical applications.