The skin is a highly complex organ that provides a wide variety of functions, including protection against toxins, pathogenic organisms and physical insults. When there is a breach in this very important barrier, it becomes clear that the skin is also an immune organ. There is a yin and a yang to the role of inflammation in wound healing. Although most of us take it for granted, normal wound healing requires a rapid inflammatory response with quick resolution. When this basic process is disrupted, either due to systemic illness or local factors, pathologic abnormalities in wound healing occur. This chapter will examine the normal inflammatory response as well as the factors that lead to chronic non-healing wounds. Identification of abnormal cellular and molecular immune responses may lead to targeted therapeutic strategies that promote harmony in the wound healing symphony.