Suicidal behavior has neurobiological determinants independent of the psychiatric illnesses with which it is associated. We have found that some patients with major depression are vulnerable to acting on suicidal impulses. This vulnerability results from the interaction between triggers or precipitants and the threshold for suicidal behavior. An important factor in setting an individual's threshold for acting on suicidal impulses is brain serotonergic function. Serotonin function has been shown to be lower in suicide attempters by studies measuring serotonin metabolites in cerebrospinal fluid and studies of prolactin response to fenfluramine. Postmortem studies of suicide victims also reveal decreased serotonin activity in the ventrolateral prefrontal cortex. New neuroimaging paradigms, such as positron emission tomography (PET), offer an opportunity to visualize serotonin function in vivo in a more direct way than has previously been available. This technology may provide the possibility of timely therapeutic intervention in patients at high risk for suicide.