Major depressive disorder (MDD) is a major health concern with alarming rates of completed suicide. Thus, it is important to understand the pathophysiology of this disorder. In addition, disturbingly high rates of relapse and low rates of recovery make it urgent not only to develop targeted treatments but to identify biomarkers that can predict treatment response for individual patients. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by modulating translation, mRNA degradation or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Several recent studies have suggested the possible role of miRNAs in synaptic plasticity, neurogenesis, and stress response, all implicated in MDD. Emerging studies showthe direct role of miRNAs in the development of depression phenotype. More recently, the role of miRNAs in prognosis and treatment response is being considered for various disease pathophysiology, including MDD. The review discusses the recent studies demonstrating the role of miRNAs in MDD and whether miRNA can be used as a biomarker for MDD pathogenesis and treatment response.