The advent of the selective serotonin reuptake inhibitors (SSRIs) and the dual serotonin noradrenaline reuptake inhibitors (SNRIs) has been welcomed by patients, largely owing to their superior tolerability profile as compared to older antidepressants. However, individual SSRIs and SNRIs do not have the same effect on all patients all the time. The characteristics of fluvoxamine, paroxetine, and milnacipran used for the treatment of depression are reviewed in this paper. Fluvoxamine, paroxetine, and milnacipran each have their own optimal doses and appropriate treatment durations. Gender, age, first episode or recurrence, family history, psychiatric symptoms, and manic change rate were considered as predictors of the response to fluvoxamine, paroxetine, and milnacipran. Fluvoxamine showed a good response in young adults and in those with a first episode. Paroxetine showed a good response in first episode patients. Milnacipran showed a good response in older patients, males, first episode patients, and those with agitated depression. Paroxetine use was associated with a higher rate of mania induction than fluvoxamine and milnacipran. Knowing these characteristics should help guide clinicians in selecting antidepressants for their patients with depression.