Traffic accidents, terminal cancer, heart attacks, earthquakes and tsunamis …… are always too many and too bleak ways for life to pass away. But did you know that in addition to these helpless natural and man-made disasters, there are many people who end their lives in a rather heartbreaking way – by suicide. According to research statistics, in 2011 alone, nearly 40,000 people died by suicide in the United States, while the number of suicides worldwide is close to one million. Suicide, has become a leading cause of accidental death worldwide. Suicide is considered to be an extreme behavior of susceptible people stimulated by specific life events or by the onset of mental illness. The susceptibility traits of these populations are based on genetic risk factors, which in turn produce neurophysiological organic changes due to the accumulation of subsequent traumatic events, physical and psychological disorders, etc. Many studies have shown that suicide has a significant biological basis. Biological factors associated with suicide include the “hypothalamic-pituitary-adrenal” axis (HPA axis) and the blue spot norepinephrine system in the biological stress response, cytokines, polyunsaturated fatty acids, endogenous opioid system, neurotransmitters such as 5-hydroxytryptamine, norepinephrine, dopamine, gamma-aminobutyric acid, glutamate, etc. , molecular markers of neuroplasticity, etc. Suicide is a complex problem in which multiple biological systems are interrelated, and the establishment of a suicide model should be a unity across multiple systems, although further research is needed on the biological components involved in this model. However, some current data suggest that dysfunction of the human stress response system, especially dysfunction of the HPA axis, is one of the most critical biological markers of suicide; and that such dysfunction may be reflected in neuroinflammatory markers, glutamate function, and plasticity of nerve cells and intracerebral circuits. Dysfunction of the CRH/HPA axis (CRH-HPA) can affect many systems (e.g., 5-hydroxytryptamine, opioid system, glutamate system, inflammatory pathways, lipid status, neuroplasticity, neurogenic system) in association with suicide. Thus, we can also see that suicide is not a behavior that can be defined or predicted by a single factor, but a complex situation with multiple biological markers associated with multiple systems. In summary, the most prominent biological markers of suicide are the stress response system and its downstream responses, as well as abnormalities in the function of the 5-hydroxytryptamine system. Given the complexity of the biological factors of suicide, future research may examine more parallel studies of multiple biological markers of suicide and attempt to isolate the specific role of each marker.