Most chronic wounds can be classified into three major types: pressure ulcers, venous ulcers, and diabetic ulcers. The authors propose a unifying hypothesis of chronic wound pathogenesis based on four main causative factors: local tissue hypoxia, bacterial colonization of the wound, repetitive ischemia-reperfusion injury, and an altered cellular and systemic stress response in the aged patient. Traditional strategies for the treatment of chronic wounds have shown limited success. The authors explore potential treatment regimens specifically aimed at each individual determinant of chronic wound pathogenesis. Furthermore, they explore a combined therapeutic approach that collectively targets all the components of chronic wound pathology. These innovative ideas and therapies could be of substantial interest for clinicians and researchers, while further offering significant benefit to patients with chronic wounds.