The ability to adapt to stress is an important defensive function of a living body, and impairment of this ability may contribute to some stress-related disorders. Thus, the examination of brain mechanisms involved in stress adaptation could help to pave the way for new therapeutic strategies for stress-related affective disorders, such as anxiety and depression. The present review focuses on the roles of brain serotonin (5-hydroxytryptamine; 5-HT) neuronal systems, and especially 5-HT1A receptors, on the development of stress adaptation. Although animals exposed to acute stress stimuli exhibit various stress responses, these disappear after chronic exposure to the same type of stress stimuli, indicating the development of stress adaptation. The evidence obtained from studies using stress-adapted animals suggests that maintenance of the 5- HT neuronal response to stress stimuli together with down-regulation of 5-HT1A autoreceptors, as well as up-regulation of postsynaptic 5-HT1A receptors, may contribute to the formation of stress adaptation. In contrast, disappearance of the 5- HT neuronal response to stress stimuli and dysfunction of postsynaptic 5-HT1A receptors are observed in animals subjected to inadaptable stress stimuli. Furthermore, exogenous activation of 5-HT1A receptors by injection of 5-HT1A receptor agonists facilitates the ability to adapt to stressful situations, confirming that 5-HT1A receptors play an important role in the formation of stress adaptation. These findings suggest that the brain 5-HT neuronal system, and particularly 5- HT1A receptors, may play a key role in the development of stress adaptation, and maintenance of this system may be particularly important for preventing and / or treating affective disorders.