Generalized anxiety disorder (GAD) is a relatively prevalent and disabling condition. Duloxetine, an inhibitor of both serotonin and norepinephrine, was approved by the US FDA in 2007 for the treatment of GAD. Short-term efficacy of duloxetine in dosages of 60-120 mg/day has been established in four double-blind, placebo-controlled trials of 9-10 weeks duration. Duloxetine has also been found to meet rigorous criteria for noninferiority in comparison with venlafaxine in GAD. Duloxetine has shown superiority on measures of functioning and quality of life and, compared with placebo treatment, it reduces painful physical symptoms common in GAD patients. Continuation treatment for acute treatment responders was found to prevent relapse of GAD to a significantly greater degree than placebo. In all acute and long-term trials, duloxetine was well-tolerated. This body of research suggests that duloxetine should be one of the options considered as a first-line treatment for GAD.