A growing body of researches support a role for dysfunction of serotoninergic, noradrenergic, and dopaminergic systems in the neurobiological processes involved in major depression disorder (MDD) and anxiety disorders. The physiological changes underlying abnormal signaling of 5-HT, NE, and DA may be due to either reduced presynaptic release of these neurotransmitters or aberrant signal transductions, and thus contributing to the alterations in regulation or function of receptors and/or impaired intracellular signal processing. Animal models demonstrate crucial responsiveness to disturbance of 5-HT, NE, and DA neurotransmissions. Post-mortem and biochemical studies have shown altered concentrations of 5-HT, NE, and DA metabolites in brain regions that contribute importantly to regulation of mood and motivation in patients with MDD or Anxiety. Neuroimaging studies have found abnormal 5-HT, NE, and DA receptors binding and regulation in regard to receptor numbers. Medications that act on 5-HT, NE, and DA neurons or receptors, such as SSRIs and SNRIs, show efficacy in both MDD and ADs. The overlapping treatment response presumably suggests a common mechanism underlying the interaction of these disorders. In this paper, we reviewed studies from multiple disciplines to interpret the role of altered neurotransmitters such as 5-HT, NE and DA in both MDD and Anxiety.