Escitalopram (escitalopram oxalate; Cipralex, Lexapro), a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD), demonstrates a highly selective and potent, dose-dependent inhibition of the human serotonin transporter, inhibiting serotonin reuptake into presynaptic nerve terminals and thus increasing serotonergic activity in the CNS. With regard to primary endpoints (such as improved scores on the Montgomery-Asberg Depression Rating Scale [MADRS] and the Hamilton Depression Rating Scale [HAM-D]), escitalopram was generally more effective than placebo, at least as effective as citalopram, and generally at least as effective as other comparator drugs, including the SSRIs fluoxetine, paroxetine and sertraline, the serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) venlafaxine extended release and duloxetine, and the aminoketone bupropion in adult patients with MDD in short-term, well designed trials. Moreover, it demonstrated a rapid onset of antidepressant action. Escitalopram was also found to be cost effective in several studies, dominating other SSRIs and venlafaxine extended release. Maintenance therapy is commonly required to prevent recurrence of depression. Long-term trials corroborated short-term results, with escitalopram demonstrating greater efficacy than placebo in relapse prevention. Additionally, escitalopram was at least as effective as citalopram, paroxetine and duloxetine in long-term comparative trials. Escitalopram has a predictable tolerability profile with generally mild to moderate and transient adverse events, and a low propensity for drug interactions. Sexual dysfunction with escitalopram treatment appeared to occur to a similar or lower extent to that with paroxetine (another SSRI), to a similar or greater extent to that with the SNRI duloxetine, and to a greater extent than that with the aminoketone bupropion. Thus, escitalopram is an effective and generally well tolerated treatment for moderate to severe MDD. Escitalopram, like other SSRIs, is an effective first-line option in the management of patients with MDD.