Escitalopram, a selective serotonin reuptake inhibitor (SSRI) was recently approved by the United States Food and Drug Administration (FDA) for the treatment of major depression. This chapter reviews preclinical and clinical studies with escitalopram, focusing on its therapeutic profile of action and tolerability. Escitalopram is the S-enantiomer of the racemic SSRI citalopram. It has been proposed that the S-enantiomer of citalopram is the isomer that holds antidepressant efficacy, and that the R-enantiomer is clinically inactive; preclinical and clinical data support this. Based on in vitro radioligand binding data, escitalopram is the most selective SSRI available. Hypotheses that escitalopram has a more rapid onset of action or fewer adverse effects than citalopram have not yet been fully documented in published studies, although its profile is at least comparable to citalopram. Escitalopram is more effective than placebo in the treatment of major depression and as effective as other SSRIs, including citalopram. Comparable to other SSRIs, it is well tolerated, safe in overdose and has a low incidence of adverse effects or drug interactions.