Eicosanoids are bioactive lipids derived from arachidonic acid and other polyunsaturated fatty acids (PUFAs) that regulate homeostatic and inflammatory processes. They are involved in immune responses, with both pro-inflammatory and anti-inflammatory roles. Recent advances in lipidomics have revealed the complexity of eicosanoid signaling, including their roles in resolving inflammation. Eicosanoids are produced through various enzymatic pathways, including cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes, and their metabolism is tightly regulated by phospholipase A2 (PLA2) enzymes. The interaction between these pathways is crucial for immune responses, as they influence inflammation, resolution, and tissue homeostasis. Eicosanoids are involved in the production of specialized pro-resolving mediators (SPMs), such as lipoxins, resolvins, and protectins, which help in resolving inflammation. These mediators are generated through the action of various enzymes and are essential for tissue repair and immune regulation. The study of eicosanoid biosynthesis and signaling has led to the development of targeted therapies, including NSAIDs and inhibitors of specific pathways like COX-2 and 5-LOX. However, the complexity of eicosanoid pathways and their interactions with other signaling molecules make it challenging to develop effective treatments. Lipidomics has provided new insights into eicosanoid metabolism, allowing for the identification and quantification of various eicosanoid species. This approach has enhanced our understanding of their roles in disease and has led to the discovery of new therapeutic targets. The integration of lipidomics with other omics approaches, such as genomics and proteomics, is helping to unravel the complex interactions between eicosanoids and other signaling molecules. This knowledge is crucial for developing more effective treatments for inflammatory and metabolic diseases. The review highlights the importance of eicosanoids in infection and inflammation, emphasizing their dual roles in both promoting and resolving immune responses. The study of eicosanoid signaling has revealed the need for a more nuanced approach to therapeutic intervention, focusing on specific mediators rather than broad pathway inhibition. The use of lipidomics and other advanced techniques is expected to further refine our understanding of eicosanoid biology and improve the development of targeted therapies.Eicosanoids are bioactive lipids derived from arachidonic acid and other polyunsaturated fatty acids (PUFAs) that regulate homeostatic and inflammatory processes. They are involved in immune responses, with both pro-inflammatory and anti-inflammatory roles. Recent advances in lipidomics have revealed the complexity of eicosanoid signaling, including their roles in resolving inflammation. Eicosanoids are produced through various enzymatic pathways, including cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes, and their metabolism is tightly regulated by phospholipase A2 (PLA2) enzymes. The interaction between these pathways is crucial for immune responses, as they influence inflammation, resolution, and tissue homeostasis. Eicosanoids are involved in the production of specialized pro-resolving mediators (SPMs), such as lipoxins, resolvins, and protectins, which help in resolving inflammation. These mediators are generated through the action of various enzymes and are essential for tissue repair and immune regulation. The study of eicosanoid biosynthesis and signaling has led to the development of targeted therapies, including NSAIDs and inhibitors of specific pathways like COX-2 and 5-LOX. However, the complexity of eicosanoid pathways and their interactions with other signaling molecules make it challenging to develop effective treatments. Lipidomics has provided new insights into eicosanoid metabolism, allowing for the identification and quantification of various eicosanoid species. This approach has enhanced our understanding of their roles in disease and has led to the discovery of new therapeutic targets. The integration of lipidomics with other omics approaches, such as genomics and proteomics, is helping to unravel the complex interactions between eicosanoids and other signaling molecules. This knowledge is crucial for developing more effective treatments for inflammatory and metabolic diseases. The review highlights the importance of eicosanoids in infection and inflammation, emphasizing their dual roles in both promoting and resolving immune responses. The study of eicosanoid signaling has revealed the need for a more nuanced approach to therapeutic intervention, focusing on specific mediators rather than broad pathway inhibition. The use of lipidomics and other advanced techniques is expected to further refine our understanding of eicosanoid biology and improve the development of targeted therapies.