Major depressive disorder is a debilitating disease that imposes significant burden not only on patients but also on society for its high prevalence and association with serious consequences such as suicide and substantial negative impact on social health, with both direct and indirect considerable costs worldwide. Selective serotonin reuptake inhibitors （SSRIs）treatment was introduced 12 years ago and reduced morbidity of major depressive disorder with a favorable side effect profile. However, unfortunately, not all individuals benefit from treatment and 30―40% of patients do not show a complete response to treatment. Clinical guideline does not show which antidepressant is the most appropriate to the patient just in front of you in clinical setting but simply suggest ‘use the new antidepressant such as SSRI, SNRI,mirtazapine as first line therapy’or ‘be vigilant for side effect’. In this paper, I summarized the considerable evidence such as meta-analysis, guideline and double blind randomized controlled trial to detect the most appropriate pharmacotherapy as firstline and second or later therapy including treatment resistant depression from the some specific factors point of view; specific feature of symptom, ethnicity and genetic feature. And I also would like to refer the possibility of some factors that predict antidepressant treatment response.