Results from a range of studies using diverse designs and both postmortem and in-vivo techniques show impairments in the serotonin neurotransmitter system and the hypothalamic–pituitary–adrenal (HPA) axis stress-response system in the vulnerability to suicidal behaviour. The involvement of serotonin in the development of suicidal behavior is well known since the 1970s when low levels of serotonin metabolites in the cerebrospinal fluid of suicide attempters were demonstrated. This involvement has been confirmed in numerous subsequent postmortem and in-vivo neuroimaging studies. For example, molecular imaging studies have localized lower binding to the serotonin transporter in areas of the brain, such as the ventromedial prefrontal cortex, which are known to be involved in decision-making processes. Serotonergic impairments may also manifest as impaired cognitive control of mood, pessimism, impaired problem solving, increased reactivity to negative social signs, excessive emotional pain, and suicidal ideation, leading to suicidal behavior.