Citalopram (Celexa) and its pharmacologically active enantiomer, S-citalopram (Lexapro), are among the most selective serotonin (5-HT) reuptake inhibitors available. Both drugs are widely prescribed and have been shown in large-scale controlled trials to be effective in the treatment of depression; S-citalopram has also been shown in large-scale controlled trials to be effective in the treatment of anxiety disorders. In addition, both drugs are well tolerated in patients and show a low potential for pharmacokinetic drug interactions. Citalopram and S-citalopram have similar efficacy in the treatment of depression, with some studies suggesting a modest superiority of S-citalopram over citalopram in some measures of efficacy, including a possibly faster onset of therapeutic effect for S-citalopram. Antagonism of the effects of S-citalopram by R-citalopram has been invoked to explain the purported therapeutic differences between the two drugs. In addition, the affinity of citalopram for histamine receptors appears to reside in the R-enantiomer, suggesting that S-citalopram has a decreased potential for antihistaminergic side effects. Whether the postulated superiority of S-citalopram over citalopram is clinically meaningful in psychiatric practice requires further study.