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full-thickness skin defects remain a reconstructive challenge. Novel regenerative modalities can aid in addressing these defects. A literature review of currently available dermal and epidermal regenerates was performed. The mechanism and application for each skin substitute was analyzed to provide a guide for these modalities. Available epidermal substitutes include autografts and allografts and may be cultured or noncultured. Dermal regenerate templates exist in biologic and synthetic varieties that differ in the source animal and processing. Epidermal and dermal skin substitutes are promising adjunctive tools for addressing certain soft tissue defects and have improved outcomes in reconstructive procedures. The following article provides a comprehensive review of the biologic materials available and the types of complex wounds amenable to their use.