"Lipid mediators" represent a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. They are exported extracellularly, bind to their cognate G protein-coupled receptors (GPCRs) to transmit signals to target cells, and are then sequestered rapidly through specific enzymatic or non-enzymatic processes. Because of these properties, lipid mediators can be regarded as local hormones or autacoids. Unlike proteins, whose information can be readily obtained from the genome, we cannot directly read out the information of lipids from the genome since they are not genome-encoded. However, we can indirectly follow up the dynamics and functions of lipid mediators by manipulating the genes encoding a particular set of proteins that are essential for their biosynthesis (enzymes), transport (transporters), and signal transduction (receptors). Lipid mediators are involved in many physiological processes, and their dysregulations have been often linked to various diseases such as inflammation, infertility, atherosclerosis, ischemia, metabolic syndrome, and cancer. In this article, I will give an overview of the basic knowledge of various lipid mediators, and then provide an example of how research using mice, gene-manipulated for a lipid mediator-biosynthetic enzyme, contributes to life science and clinical applications.