Evidence-based guidelines for the pharmacologic management of patients with generalized anxiety disorder (GAD) recommend initial treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). However, response rates to initial treatment with an SSRI or SNRI can be disappointing, and it remains impossible to predict reliably which patients will respond positively or negatively to treatment. Due to the dearth of longitudinal studies of outcome in GAD and the relatively small number of placebo-controlled relapse prevention studies, the optimal duration of treatment after a satisfactory response to acute treatment is still uncertain. Furthermore, there have been few studies on the management of patients who do not respond to initial treatment. Also, there is a clear need for further randomized controlled trials of augmentation treatment in patients who do not respond to SSRI, SNRI, or other initial pharmacologic approaches. Future guidelines will be influenced by emerging data with both established and novel drug treatments, and through better identification of patient groups that are likely to respond preferentially to particular interventions.