Specific serotonin and norepinephrine reuptake inhibitors are a relatively recent class of antidepressants which have specificities making them a therapeutic choice. They are characterized by a mixed action on both major neuroamines of depression: norepinephrine and serotonin. The double polarity of the reuptake inhibition of serotonin and norepinephrine ensures a profile of effectiveness comparable to tricyclic antidepressants and higher than selective serotonin reuptake inhibitors, especially in severe depression. The absence of affinity for muscarinic, histaminic and alpha1-adrenergic receptors and the absence of action on monoamine oxidase limits their adverse effects and allows them to be better tolerated than tricyclic antidepressants and similar to selective serotonin reuptake inhibitors. Currently, two drugs of this class are available, milnacipran and venlafaxine, but several more are in development. They are active on depressive symptoms, as well as on certain comorbid symptoms (anxiety, sleep disorders) frequently associated with depression. Serotonin and norepinephrine reuptake inhibitors allow an improved rate of response and a significant rate of remission, decreasing the risk of relapse and recurrence in the medium and long term. Due to their good tolerance, they can also be prescribed for long-term treatment and in high doses in refractory depression or with strong potential of relapse. For all these reasons, one can reasonably conclude that serotonin and norepinephrine reuptake inhibitors represent the therapeutic of choice in depression and that their prescription is likely to strongly increase in the years to come.