Chronic wounds and ulcers present increasing therapeutic challenges as our population ages. Some chronic wounds become locked in the inflammatory phase and are unable to progress to form granulation tissue. Evidence is now emerging that activated protein C (APC) contributes to wound repair through a complex mechanism that involves inhibition of inflammation, angiogenesis, antiapoptotic properties, and reepithelialization. In this series of 4 cases of nonhealing lower limb skin ulcers, Whitmont et al demonstrate that weekly topical APC application can produce a rapid and sustained wound-healing response. These data present compelling evidence that APC provides a safe, efficacious, and well-tolerated therapeutic option for recalcitrant chronic wounds.