Intervertebral disc degeneration (IVDD) has been one of the most significant contributors to low back pain. Despite the favorable outcomes resulted from surgical intervention, early prevention and alleviation of IVDD have been a research focus. Therefore, it is particularly important to investigate the potential mechanism of IVDD. Increasing studies have suggested that multiple systems in our body are involved in the process of IVDD directly or indirectly. This article reviews the mechanism of IVDD from the perspectives of nerve, immune and endocrine systems, hoping to provide new insights into the future prevention and treatment of IVDD.