Inflammation when uncontrolled is associated with prevalent disorders such as arthritis and periodontal disease, diabetes and cardiovascular diseases. Hence mechanisms to dampen the inflammatory response and promote resolution are of immense interest. Recent evidence has prompted a paradigm shift whereby the resolution of acute inflammation is now considered a biochemically active process regulated in part by endogenous PUFA (polyunsaturated fatty acid)-derived autacoids. Among these are specialized pro-resolving mediators (SPMs) that comprise lipoxins, resolvins, protectins and maresins. SPMs are endogenous stereoselective, potent mediators that temper both the magnitude and duration of inflammatory responses. Moreover, an appreciation of these endogenous mediators and pathways that control timely resolution opens a new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation. The focus of this review is to depict recent advances on the biosynthesis and actions of these novel pro-resolving and protective lipid mediators. Collectively, these findings indicate that defective mechanisms and pathways in resolution may underlie the unchecked inflammatory phenotype(s) that characterize some prevalent human diseases.