Generalized anxiety disorder (GAD) is common in community and clinical settings. The associated individual and societal burden is substantial, but many of those who could benefit from treatment are not recognized or treated. This paper reviews the pharmacological treatment of GAD, based on findings of randomized placebo-controlled studies. Particular attention is paid to response rates to acute treatment, treatment tolerability, prediction of response, duration of treatment, and further management of patients who do not respond to initial treatment approaches. On the basis of their proven efficacy and reasonable tolerability in randomized placebo-controlled trials, recent evidence-based guidelines for pharmacological management have recommended initial treatment with either a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor, although there is also good evidence for the efficacy of pregabalin and quetiapine. It is difficult to predict reliably which patients will respond well to pharmacological treatment, but response to antidepressants is unlikely if there is no evidence of an onset of effect within 4 wk. The small number of placebo-controlled relapse-prevention studies causes uncertainty about the optimal duration of treatment after a satisfactory initial response, but continuing treatment for at least 12 months is recommended. There have been few investigations of the further management of patients who have not responded to first-line treatment, but switching to another evidence-based treatment, or augmentation approaches may be beneficial.