Psychosocial stress is a risk factor for psychiatric disorders, including depression and anxiety, and chronic pain, whereas chronic pain is also closely related to the development of psychiatric disorders. However, the pathological mechanisms of stress-triggered psychiatric disorders and chronic pain are unknown, and their effective treatments have not been established. Recently, the advances in analytical techniques for fatty acids and their metabolites have made it possible to comprehensively measure changes in fatty acid composition in various cells and organs using the lipidomics approach, and to visualize the localization of phospholipids, fatty acids, and other lipid mediators using imaging mass spectrometry. Many researchers have focused on understanding the differences in the distribution of phospholipids, fatty acids, their lipid metabolites in cells and organs, and the changes of fatty acid composition in various diseases. More recently, changes in the fatty acid composition and its distribution during chronic pain and stress have also been reported. We also proposed that modulation of brain fatty acid signaling could be a new therapeutic target for stress-induced chronic pain. In this review, we summarize the latest basic and clinical findings on the role of fatty acid signaling in stress-induced psychiatric disorders and chronic pain.