Predicting suicide is difficult due to the low base rate, even in high-risk groups, and the multi-causal nature of suicidal behavior. Clinical predictors have shown low specificity. Retrospective and cross-sectional studies have identified a number of biologic anomalies associated with suicide and suicide attempt. Prospective studies provide estimates of the predictive utility of biologic measures. Here we review prospective studies of suicidal behavior and serotonergic, noradrenergic, dopaminergic and hypothalamic-pituitary-adrenocortical axis function in mood disorders. The most promising biologic predictors are low CSF 5-HIAA and HPA axis dysfunction as demonstrated by dexamethasone non-suppression that are each associated with about 4.5 fold greater risk of suicide.