In a review of the current literature, we identified (1)H MRS studies of major depressive disorder (MDD) that examined the metabolites N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), glutamate/glutamine/gamma-aminobutyric acid-GABA (Glx), and creatine (Cr). Separate meta-analyses comparing adult and pediatric MDD patients with healthy controls were performed. For adults, 14 studies with 227 patients/246 controls for NAA, 15 studies with 240 patients/261 controls for Cho, seven studies with 96 patients/104 controls for mI, six studies with 86 patients/109 controls for Glx, and nine studies with 146 patients/173 controls for Cr were identified. There were six studies containing a total of 79 pediatric depressed patients. We performed 15 separate meta-analyses to combine results from studies with similar characteristics. Adult MDD patients had higher Cho/Cr values than controls in the basal ganglia. In contrast, three studies on Glx levels indicated significantly lower Glx levels in the frontal lobe of MDD patients. The review indicated increased Cho/Cr in the basal ganglia in MDD and no alteration of NAA, suggesting an increased membrane turnover in MDD without a neurodegenerative outcome. Lower Glx levels in depressed patients in contrast to a likely hyperglutamatergic state in bipolar disorder may implicate a different pathophysiological ground in MDD.