Resolution of the acute inflammatory response is an active and regulated dynamic process essential for restoring normal physiological functions and tissue repair. This biochemical process requires a coordinated interplay involving immune cells, molecular signals, and lipid mediators that work together to contain harmful stimuli following tissue injury or infection. Biosynthesized from omega-3 and omega-6 essential fatty acids, specialized pro-resolving mediators (SPMs) play a crucial role in actively facilitating the resolution of inflammation, promoting tissue repair, and modulating immune responses. These bioactive lipid mediators—namely, lipoxins, resolvins, protectins, and maresins—not only counteract pro-inflammatory signals but also enhance innate mechanisms of healing and regeneration. Dysregulation of this system has been implicated in the pathogenesis of a wide range of acute and chronic diseases, including cardiovascular disorders, neuroinflammatory conditions, and cancer to name but a few. Understanding the molecular mechanisms of SPMs provides valuable insights into their therapeutic potential, both as novel pro-resolving agents and as biomarkers. This chapter briefly reviews and highlights this growing and emerging field of pro-resolving lipid mediators, focusing on their biosynthesis, functions, and clinical implications, as well as underscoring their role in inflammation resolution and promise for future biomedical use.