AbstractTrauma or infection can result in tissue damage, which needs to be repaired in a well‐orchestrated manner to restore tissue function and homeostasis. Lipid mediators derived from arachidonic acid (termed eicosanoids) play central and versatile roles in the regulation of tissue repair. Here, I summarize the current state‐of the‐art regarding the functional activities of eicosanoids in tissue repair responses during homeostasis and disease. I also describe how eicosanoids are produced during tissue damage and repair in a time‐, cell‐ and tissue‐dependent fashion. In particular, recent insights into the roles of eicosanoids in epithelial barrier repair are reviewed. Furthermore, the distinct roles of different eicosanoids in settings of pathological tissue repair such as chronic wounds, scarring or fibrosis are discussed. Finally, an outlook is provided on how eicosanoids may be targeted by future therapeutic strategies to achieve physiological tissue repair and prevent scarring and loss of tissue function in various disease contexts.