A review with 206 references. The introduction in therapy of selective serotonin reuptake inhibitors (SSRIs) has brought forth many improvements in the treatment of depression, due to their proven clinical efficacy, good tolerability and relative safety. With respect to classic tricyclic antidepressants (TCAs), the SSRIs show little affinity for dopamine (D₂), serotonin (5-HT_1A, 5-HT_2A), adrenergic muscarinic and histamine (H₁) receptors. Despite their common mechanism of action, the main SSRIs, i.e. citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, differ in chemical structure, pharmacokinetics and metabolism. The SSRIs undergo extensive metabolism in the liver by cytochrome P450 isozymes, although other paths of metabolism are possible. Moreover, they inhibit cytochrome P450 isozyme CYP2D6 with different potencies, with paroxetine being the most potent and fluvoxamine the least potent. These pharmacokinetic differences determine high interindividual variability in plasma antidepressant concentrations and drug-drug interactions, above all with those drugs (e.g TCAs) that are metabolised by the same enzymes. The main pharmacodynamic and pharmacokinetic properties of the five most important SSRIs, as well as their pharmacological interactions, are described in this review.