Advanced magnetic resonance imaging techniques, such as proton magnetic resonance spectroscopy (H-MRS), have helped to further understanding of the pathophysiology of major depressive disorder (MDD) and to shed light on mechanisms underlying the therapeutic response. Potential complications of MDD therapy constitute an important area of research. Interruption of the absorption of serotonin reuptake inhibitors (SSRIs) is associated with discontinuation syndrome, while electroconvulsive therapy (ECT) can lead to transient and persistent anterograde amnesia. This paper reviews studies, since 1994, that have used H-MRS to evaluate adverse effects and complications of MDD treatment, either with ECT or SSRIs. Three articles have been published on adverse effects and complications of MDD treatment and H-MRS. Two focused on the ECT-induced memory deterioration and showed no sign of hippocampal atrophy in MDD patients with a residual memory deterioration after ECT, but a significant mean increase of the signal from Cho-containing compounds bilaterally, possibly due to an alteration of membrane turnover in the hippocampal region. The third paper showed that placebo-day Cho/Cr metabolite ratios were decreased in subjects with discontinuation syndrome, a finding that possibly reflects the dynamics of rostral anterior cingulate function. In spite of the limits deriving from the small number of papers published, our review demonstrated that H-MRS could be a useful instrument not only in evaluating therapy efficacy, but also for offering new insights into mechanisms underlying MDD treatments.