Norepinephrine (NE) is one of three catecholamine neurotransmitters in the brain and has been studied extensively in relation to the biology of suicide as well as psychiatric disorders that significantly increase the risk of suicide. NE became a candidate for the pathology of depression in the 1950s, but not because of a discovery of altered concentrations of NE in depressed patients or suicide victims. Instead, NE was one of the neurotransmitters along with dopamine and serotonin that was directly affected by newly discovered antidepressant drugs. Since that time, NE has been one of the most studied neurotransmitters with regard to depression biology and suicide, second only to serotonin. However, interest in the role of NE in suicide and depression has dwindled considerably over the past 10 years. In fact, interest in monoamines appears to be waning overall, possibly driven by a push by the National Institutes of Health for paradigm shifts in understanding psychiatric disease biology. The move away from interest in the monoamines is also being driven by high-throughput technologies such as microarrays, which divert investigators from traditional disease candidates to novel proteins and pathways. Despite the current trends, evidence that points to dysfunction in the central noradrenergic system in depression and suicide is very strong and it remains quite possible that deficits in NE signaling may lie at the very root of psychiatric disorders that contribute to suicide. This chapter reviews the neurobiology and functional output of the brain noradrenergic system in relation to the potential involvement of NE in depression and suicide.