Eicosanoid is a collective term for oxygenated metabolites of C20 polyunsaturated fatty acids. As seen in mammals, eicosanoids play crucial roles in mediating various physiological processes, including immune responses, in insects. Upon microbial pathogen infection, non-self recognition signals are propagated to nearly immune effectors such as hemocytes and fat body using various immune mediators, in which eicosanoid signals act as the ultimate downstream mediator. The chemical diversity of eicosanoids may operate to mediate various immune responses. Some entomopathogenic bacteria suppress eicosanoid biosynthesis, which inhibits host insect immunity and promotes their pathogenicity. This review introduces immune responses mediated by various eicosanoids. Then it explains the cross-talks of eicosanoids with other immune mediators including cytokines, biogenic monoamines, and nitric oxide to clarify the complexity of insect immune mediation. Finally, we highlight the biological significance of eicosanoids by demonstrating bacterial pathogenicity inhibiting a key enzyme – phospholipase A2 – in eicosanoid biosynthesis using their secondary metabolites to defend host insect immune attack.