Morphogenesis provides fundamental understanding of biological processes during the formation, maintenance, degeneration, and regeneration of tissues or organs. The emphasis of morphogenesis in a regenerative engineering approach is focused on studying the implications of regulated cellular activity in the formation of multicellular arrays and consequent complex tissue systems. The classic example of morphogenesis is limb regeneration. In urodeles the epidermal cells around the wound have the ability to migrate into the wound site, cover the mesenchymal tissues, and form a wound epidermis with migration of fibroblast underneath. This involves the formation of a local growth zone, or blastema, at the plane of amputation. The blastemal cells are highly unique and exhibit several markers that are not exhibited by differentiated mesenchymal cells. In most of the urodeles the local reversal of the differentiated state of the cells (dedifferentiation) in response to the amputation occurs naturally. The blastemal cells then proliferate to produce a conical mound of cells which progressively exit from the cell cycle to differentiate into cartilage, connective tissue and muscle of the regenerating limb. In the case of humans, however, the epidermal appendages that have been lost at the site of the damage will not regenerate and healing of the wound will leave a connective tissue scar, where the collagen matrix has been poorly reconstituted. The “bottom up” approach to limb regeneration is seeking to determine why humans lack the ability to regenerate lost organs and whether epimorphic regeneration seen in urodele amphibians could be translated to human regenerative medicine. Alternatively, one could approach limb regeneration from the “top down” where the limb structure as a whole is considered, developed tissue by tissue, and then integrated into one contiguous structure.