The development of new therapies for treatment of chronic wounds has not matched the availability of treatment modalities forecast by the pharmaceutical industry. This is attributable in large part to difficulties encountered in clinical trials as well as in isolating study design variables. Our hypothesis attempts to address this shortcoming. We are proposing that chronic wound pathogenesis is based on 3 fundamental factors: the cellular and systemic changes of aging, repeated ischemia-reperfusion injury, and bacterial colonization with resulting inflammatory host response. The derivation of this hypothesis is founded on the observation that the 3 primary categories of chronic wounds—pressure ulcers, diabetic ulcers, and venous ulcers, which are the overwhelming majority of chronic wounds—have these common causative factors. Our hypothesis incorporates major implications for treatment modalities based on these factors. Addressing the first issue, the cellular and systemic changes of aging, Regranex (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a platelet-derived growth factor drug, has shown great promise. Additional treatment modalities that address the second and third problems, repeated ischemia-reperfusion injury and bacterial colonization, include vacuum-assisted closure, warming of local tissue, and water irrigation using pulsed lavage. Additionally, treatment comprising a combination of these approaches has demonstrated success.