Bipolar disorder is considered an important public health problem in the world. The depressive phase is the most important in terms of frequency, duration, and impairment of the quality of life. Common treatment of bipolar depression usually includes antidepressants, mood stabilizers and antipsychotics in different combinations, despite not having a specific indication for that. Quetiapine is the first drug in Europe that has obtained a specific indication for the treatment of bipolar depression, due to a pharmacologic profile that makes it to act on the three neurotransmitter systems involved in bipolar depression neurobiology. Regarding the dopaminergic pathway, quetiapine leads to an increasing of prefrontal dopamine release by antagonism of5-HT2A receptors, partial agonist of 5-HT1A and antagonism of a2 adrenoceptors. Quetiapine also enhances the serotoninergic transmission by increasing the density of receptors5-HT1A in the prefrontal cortex and by antagonism of 5-HT2A receptors and a2 adrenoceptors. On the other hand, norquetiapine, the main active metabolite of quetiapine, actsas a 5-HT2C antagonist and is a potent inhibitor of norepinephrine transporter (NET). NET inhibition leads to an increase of noerpinephrine in the synapse, and together with the increase of prefrontal dopamine and serotonin, could explain the antidepressive effect demonstrated by quetiapine in several clinical trials. Quetiapine’s action on glutamatergicand GABAergic receptors represents an interesting object of research, together with a potential neuroprotective effect that have already been observed in animal models.