Various antidepressants and anxiolytic agents have proved to be effective as short-term therapy for generalized anxiety disorder (GAD) and other anxiety disorders. However, less is known about their efficacy in the long-term treatment of GAD. This gap in our knowledge poses a problem for physicians, who treat GAD over several months or years. More information from long-term, placebo-controlled studies of the efficacy of drug therapy for GAD will help clinicians in treatment planning. Recently, the anxiolytic effectiveness exhibited by venlafaxine extended release (venlafaxine XR) in short-term, placebo-controlled studies of nondepressed patients was confirmed in 2 long-term, placebo-controlled trials. Venlafaxine XR maintained its efficacy for up to 6 months. Compared with placebo, it demonstrated statistically significant efficacy when administered once daily in doses ranging between 37.5 and 225 mg. In addition, the incidence of adverse events was low and generally comparable to that for placebo. In light of these results, venlafaxine XR has a unique role in the long-term treatment of GAD.