Anxiety frequently coexists with depression, either as a comorbid anxiety disorder or as anxiety symptoms accompanying a primary depressive disorder. Effective therapy for the treatment of depressive illness must include a consideration of anxiety symptoms, since anxiety has been estimated to be present in up to 96% of patients with depressive illness. Available data also indicate that depressed patients with significant anxiety may be at greater risk for suicide. Of particular clinical importance are symptoms of somatic anxiety: they are present in up to 86% of depressed patients, and the failure to treat them effectively can diminish the ability of a patient to function. Since the overall prognosis for recovery from a major depressive episode is less than optimal in patients with significant anxiety, treatments that can provide an effective and early relief of both depressive and anxiety symptoms are of paramount importance. Drugs with serotonin reuptake inhibition (such as selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs]) may produce transient increases in anxiety symptomatology presenting as jitteriness, agitation, insomnia, and gastrointestinal symptoms when treatment is initiated. Mirtazapine has intrinsic receptor-blocking properties (in particular, serotonin-2 [5-HT2] receptor blockade) that can be linked to an early relief of anxiety symptoms during the treatment. The available data show that mirtazapine is superior to placebo in depressed patients with high baseline anxiety and/or agitation. Furthermore, mirtazapine was statistically significantly superior to both citalopram and paroxetine in alleviating anxiety symptoms early in treatment as assessed by changes from baseline on the Hamilton Rating Scale for Anxiety or the Hamilton Rating Scale for Depression anxiety/somatization factor, respectively. Mirtazapine provides early and effective relief of both depressive and anxiety symptoms, reducing the need for polypharmacy. These therapeutic actions of mirtazapine persist throughout the course of treatment.