For TCAs there is a strong rationale for drug level monitoring in clinical therapy. Therapeutic drug concentration ranges have been established in controlled studies with NT, imipramine, and AT. It has been shown that by appropriate choice of antidepressant and close monitoring of drug levels, treatment with antidepressants in elderly and other risk patients can be carried out effectively and safely, reducing the use of electroconvulsive therapy. Finally, the practical clinical use of antidepressant concentration measurements is now feasible and not expensive, and the analytical procedures can be established in most hospital settings. On the basis of these premises the following can be concluded: Plasma level monitoring should be used as a routine for imipramine, NT, and AT. Further plasma level studies on other antidepressants and in overdose cases should be initiated. Plasma level monitoring is indispensable in clinical research on antidepressants (trials, new drugs, toxicology). Pharmacokinetic considerations may be useful to determine which receptor effects are clinically relevant in therapy and toxicology.