Current evidence-based guidelines for generalized anxiety disorder (GAD) tend to recommend initial treatment with either a selective serotonin reuptake inhibitor or a serotonin-noradrenaline reuptake inhibitor, although there is also good evidence for the efficacy of pregabalin and quetiapine. NICE guidelines recommend that cognitive behaviour therapy is reserved for patients not responding to initial interventions based on self-help and psychoeducation. The findings of a mixed treatment comparison and meta-analysis demonstrate the difficulty in establishing the relative efficacy and tolerability of pharmacological treatments. It is hard to predict which patients will respond well to pharmacological treatment, but response to antidepressants or pregabalin is unlikely if there is no onset of effect within four weeks. The value of combining pharmacological with psychological interventions is uncertain. The small number of relapse prevention studies causes uncertainty about optimal duration of treatment after a satisfactory initial response, but continuing treatment for at least twelve months is advisable. However many patients will not respond well to current interventions, and there is much room for improvement in the development of more effective and better tolerated treatments. Challenge studies in healthy volunteers, involving the inhalation of air ‘enriched’ with 7.5% CO2 provide a robust experimental medicine model of GAD and are being used to evaluate novel pharmacological and psychological interventions. In addition, advances in understanding of the potential role of neuroinflammatory factors in GAD also suggest other potential targets for pharmacological treatment.