In the past few years, a different paradigm for the understanding and treatment of chronic wounds has emerged. The term used to describe this new context in which failure to heal is viewed is "wound bed preparation". This term is revolutionizing the way we approach chronic wounds, and has allowed chronic wounds to gain independence from established models of acute injury. Within the context of wound bed preparation, impaired healing and solutions to it are being addressed in novel ways. In this report, we make use of the diabetic ulcer as an example of a chronic wound, and emphasize the pathophysiological principles, the cellular and molecular abnormalities, and the solutions offered by the new approaches of gene therapy and stem cells. The emerging view is that chronic wounds are characterized by resident cells that have undergone phenotypic changes that need to be corrected for optimal healing to occur. We have established in animal models and in humans that stem cells have the potential to bring about fundamental changes in the repair process and, ultimately, a "quantum" jump in our therapeutic success.