The development of antidepressant started from 1950's and it is based on monoamine hypothesis. Antidepressants enhance monoamine, such as serotonin, nor adrenaline and dopamine neurotransmission by blockade of monoamine transporter or monoamine oxydase. The antidepressants under clinical trials enhance those monoamine in various combinations. The development of newer antidepressants is still on pre-clinical trials. Those candidates such as neurotrophic factors and neuropeptides may show antidepressant effect without monoamine hypothesis and those are expected to overcome the limitation of existing antidepressant.