Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) may provide valuable information regarding central noradrenergic activity. In this article, we mainly reviewed about the associations between plasma MHPG levels and responses to antidepressant treatment. There exists heterogeneity of depression with regards to plasma levels of MHPG; in other words, depressed patients might be dichotomized into one group characterized by anxiety and/or perceptions of powerlessness with high plasma MHPG levels and another group characterized by psychomotor retardation with low plasma MHPG levels. In addition, it is possible that patients with lower pretreatment MHPG levels might respond to drugs that affect both noradrenergic neurons and serotonergic neurons or predominantly noradrenergic neurons. On the other hand, patients with higher pretreatment MHPG levels might respond to drugs that affect predominantly serotonergic neurons or GABAergic neurons. It is possible to predict the responses to antidepressant drugs by means of plasma MHPG levels in depressed patients.