A well-integrated host inflammatory response is essential in maintaining health and fighting disease. It is important to achieve a complete understanding of the cellular and molecular events that govern the resolution of acute inflammation. Because novel lipid-derived mediators, called resolvins and protectins in animal models, control the duration and magnitude of inflammation, the mapping of these resolution circuits may provide new ways of understanding the molecular basis of many inflammatory diseases. This article provides an overview of recent studies on resolvin and protectin biosynthesis and of advances in understanding the actions of these novel anti-inflammatory and proresolving lipid mediators. These new families of lipid-derived mediators were originally isolated from experimental murine models of acute inflammation identified during the natural spontaneous resolution phase. They are biosynthesized from omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) and possess potent anti-inflammatory, proresolving, and antifibrotic actions in vivo. Taken together, these findings suggest that defective resolution mechanisms may underlie the inflammatory phenotypes that are believed to characterize many common human diseases. The new families of endogenous proresolving and anti-inflammatory agonists constitute a new genus of anti-inflammatories.