This article reviews the data supporting the notion that there are alterations in serotonin and norepinephrine in the ventral prefrontal cortex and brainstem of suicide victims. Normal amounts of serotonin are found in terminal fields such as the dorsolateral prefrontal cortex, but serotonin responses are defective at least in the hypothalamus. Suicide victims appear to have fewer noradrenergic LC neurons, containing more of the tyrosine hydroxylase enzyme needed for transmitter synthesis. A failure of behavior restraint mechanisms involving the prefrontal cortex as a consequence of alterations in brainstem monoaminergic nuclei may result in a predisposition to suicidal behavior.