The pharmacokinetics and clinical properties of clomipramine, the classic 5-HT uptake inhibiting antidepressant is well known. Within the last years, several new and more selective serotonin uptake inhibitors have been introduced in clinical practice, including trazodone, citalopram, paroxetine, femoxetine, fluvoxamine and fluoxetine. They differ by their chemical structure, and therefore, important differences can be expected with respect to their metabolism and kinetics in man. In this presentation, the following points will be addressed: Present knowledge about their metabolism and their kinetics, taking into account that most of them are racemates, whose clinical role is only partially understood, including that of the metabolites. It will further be examined whether they are candidates for a genetic polymorphism of metabolism of the debrisoquine-spartein-dextromethorphan type. This may e.g. be suspected for fluoxetine which interferes strongly with the metabolism of tricyclic antidepressants. Finally, data of the literature will be analysed about a possible relationship between the clinical efficacy of these drugs and their plasma levels, including those of their active metabolites.