Generalized anxiety disorder (GAD) is common in community and clinical settings. The individual and societal burden associated with GAD is substantial, but many of those who could benefit from treatment are not recognized or treated. Recent evidence-based guidelines for the pharmacological management of patients with GAD have recommended initial treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), on the basis of their proven efficacy and reasonable tolerability in randomized placebo-controlled trials. However, there is much room for improvement in both the efficacy and the tolerability of treatment. Response rates to first-line treatment can be disappointing and it is hard to predict reliably which patients will respond well and which will have only a limited treatment response. Many patients worry about becoming dependent on medication, a substantial proportion experience troublesome adverse effects, and these problems limit the effectiveness of pharmacological treatments in clinical practice. The relative lack of longitudinal studies of clinical outcomes in GAD, and the small number of placebo-controlled relapse prevention studies lead to uncertainty about the optimal duration of treatment after a satisfactory initial response. There have been few investigations of the further management of patients who have not responded to first-line treatment and there is a pressing need for further augmentation studies in patients who have not responded to an SSRI or SNRI, or to other initial pharmacological approaches. Future treatment guidelines for GAD will be influenced by emerging data for established and novel pharmacological approaches, and possibly through the more accurate identification of certain patient subgroups who are likely to respond preferentially to particular interventions.