The caudal neurosecretory system (CNSS) is a unique neuroendocrine system of fish, which located at the caudal spinal cord. CNSS is the key for fish to adapt the environment. As a part of the stress system, CNSS plays comprehensive regulatory role in fish physiology and behavior. Here, we reviewed morphology and composition of this system, its main secreting products, and their role in physiological regulation and innervation since the end of the 19th century when CNSS was found. All of these will provide scientific basis for further studying on neural secretions in higher vertebrates, and even for understand the functions of neurosecretory materials in human.