The presently available selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, despite their common mechanism of action, differ in their chemical structure, metabolism and pharmacokinetics. From a clinical point of view, it is of relevance that potency to inhibit the cytochrome P450 isozyme CYP2D6 gradually decreases from paroxetine, fluoxetine, norfluoxetine, desmethylcitalopram, fluvoxamine, and sertraline down to citalopram, explaining to a great extent differences in pharmacokinetic interactions between the SSRIs and tricyclic antidepressants, which are metabolized by this enzyme. Fluvoxamine interacts with these drugs by a mechanism involving inhibition of CYP1A2, CYP3A4, and CYP2C19. Except for paroxetine, a substrate of CYP2D6, little is known about the enzymes implicated in the metabolism of SSRIs. Fluoxetine and citalopram are used as racemic drugs. Data on the stereoselectivity of their enantiomers in the inhibition of serotonin (5-HT) uptake in the animal brain, also those available on their metabolism and kinetics in humans, are presented. It may be concluded that for routine therapeutic drug monitoring, the plasma level measurement of the enantiomers of citalopram and fluoxetine is probably of little relevance. However, for the study of the structure-activity relationship between these drugs and the cerebral 5-HT transporter, the stereochemical differences of these enantiomers should be considered. In this sense, the enantiomers of these drugs could represent a promising tool to increase present knowledge.