Selective serotonin reuptake inhibitors (SSRI) are nowadays the preferred treatment for patients with depression and anxiety disorders, when compared with traditional tricyclic antidepressants. All the SSRIs were designed to selectively potentiate serotonin [5-hydroxytryptamine (5-HT)] activity through inhibition of the 5 -HT neuronal reuptake transporter. However, despite a common mode of proven antidepressant efficacy and a similar range of indications, each SSRI has individual properties, not only pharmacodinamics, but also pharmacokinetics, which contributes for different pattern of clinical indications, side effects and interactions. The authors pretended to review the differences between each SSRI, in terms of metabolism and clinical goals. They analyzed several studies published in the last years, obtained through MedLine research. The authors describe how the unique secondary binding properties of each SSRI account for clinical significant differences in tolerability and side-effects profiles, particularly in some patients. Secondary properties within the class of SSRIs include some combinations of actions at noradrenergic, dopaminergic, muscarinic, cholinergic, histaminergic and sigma receptors. In addition, most SSRI inhibit al least one of the cytochrome P450 enzymes, resulting in potential pharmacokinetics interactions with co-prescribed drugs.