Resolvins, protectins and maresins are a series of polyunsaturated fatty acid-derived molecules which play important roles in the resolution of inflammation. They are termed specialized proresolving mediators and facilitate a return to homeostasis following an inflammatory response. These molecules are currently the focus of intensive investigation, primarily for their ability to suppress inflammation in chronic disease states. Researchers have employed different synthetic approaches to assess whether various structural modifications of these compounds could provide access to future therapeutics. This review summarizes the modifications made thus far and focuses on the key structure-activity relationships which have been uncovered for resolvins, protectins, maresins and their analogues.