Major depressive disorder (MDD) is one of the most disabling disorders. Antidepressant pharmacotherapy is currently effective in approximately 70% of all treated cases; the potential superiority of a dual mechanism of pharmacological action (e.g., inhibiting the reuptake of serotonin and norepinephrine) is widely known. Duloxetine, a novel dual acting, selective serotonin and norepinephrine reuptake inhibitor, has demonstrated clinical efficacy in the treatment of MDD and general anxiety disorder (GAD). Duloxetine has been found to be safe and well tolerated, with mild-to-moderate adverse events, a favorable cardiovascular and sexual dysfunction profile, and minor influence on weight gain. The efficacy of duloxetine in the treatment of MDD has been established in randomized, double-blind, placebo-controlled studies. In addition to improving classical emotional symptoms of MDD, duloxetine has in particular beneficial effects on somatic symptoms of depression including pain. The superiority of duloxetine was shown over placebo, while comparison studies with other antidepressants showed only partial superiority. Randomized clinical trials in GAD also provide evidence for beneficial effects compared with placebo and improvement in quality of life, wellbeing and general health. Moreover, duloxetine is effective and well tolerated in the treatment of diabetic peripheral neuropathic pain and stress urinary incontinence. First results indicate that duloxetine might also be effective in the treatment of children with depression and pain. Overall, duloxetine is an interesting novel treatment option in the management of major depression and has shown efficacy in a broad range of diseases. It therefore may provide additional benefit to current therapeutic options in the treatment of psychiatric, internal, as well as urological disorders such as spinal dysfunctions. Due to duloxetine's properties, a wide range of use will be encountered in the mid-to-long term.