The rationale for the use of noradrenergic challenges, i.e., administration of psychopharmacological agents that alter noradrenergic activity, is reviewed in relation to evidence implicating the noradrenergic system as important in the etiology of treatment of the affective disorders. Recent studies employing both central noradrenergic challenges (amphetamine and clonidine) and peripheral noradrenergic challenges (tyramine, norepinephrine, and phenylephrine) are examined in terms of their behavioral, physiological, biochemical, and neuroendocrine effects. The potential utility of these challenges for clinical diagnosis and treatment planning in the affective disorders as well as for understanding possible biological factors in their etiology and emphasized. Research strategies for the future are suggested in this context.