Milnacipran is a serotonin and norepinephrine reuptake inhibitor (SNRI), with a balanced potency for the inhibition of the reuptake of the two monoamines. In this, it contrasts with venlafaxine and duloxetine which, while possessing a dual action, have a selectivity of the order of 30-fold and 10-fold respectively for the reuptake of serotonin. Milnacipran has mainly been launched in countries where the selective serotonin reuptake inhibitors (SSRIs) and venlafaxine had been established for several years. As such it has attracted relative little interest from clinician investigators as a research tool. Japan, however, represents a unique situation because in 1999 milnacipran was launched within months of the fi rst SSRI and is still the only SNRI in Japan together with only two SSRIs (a third has just been introduced). This has led to a large number of investigative clinical studies, many of which give interesting insights into the potential of milnacipran in the treatment of depression and of other disorders. This article reviews these Japanese studies with milnacipran.