The purpose of this review is to apply strict chemical and biochemical principles to observations in the clinic in an effort to gain insight into the mode of action of cadexomer iodine as it relates to the care of chronic wounds. It is clear that the primary obstacle to closure for the chronic wound is an inflammatory phase past which the wound is unable to proceed. There are two ways one might hypothesize about this situation. One hypothesis focuses on a pro-inflammatory response that is out of control due to various factors such as local tissue ischemia, bioburden, necrotic tissue, repeated trauma, etc. A second hypothesis focuses on the lack of activity of the biochemical players responsible for a pro-inflammatory response. In this case cells such as macrophages are present, but in a non-functioning state. Regardless of the hypothesis one chooses to adopt the result is the same, the wound is not able to progress past the inflammatory phase of healing and thus does not close. In the case of an out of control pro-inflammatory response, the logical therapy might be one of anti-inflammatory activity. In the case of non-functioning macrophages, the logical therapy might be one of encouraging macrophages to become active again. This review is focuses of one such therapy for which there is a great deal of in vitro and clinical support. We will see how cadexamer iodine seems to play a pro-inflammatory role. The benefits of this technology have been born out in the clinical evidence with use on chronic wounds for over a decade. With over 51 studies involving VLUs, PU, DUs and thousands of patients, cadexomer iodine has been proven to promote wound closure in chronic wounds.