The mechanisms of action (MA) of electroconvulsive therapy (ECT) in affective disorders are poorly understood. We synthesized and discussed the evidence provided by primary studies and systematic reviews in humans. There are differences in the methylation of candidate genes involved in the response to ECT. Functioning of the hippocampal serotonin receptor 5-HT1B is associated with the response in patients with major depressive disorder (PMDD), while the striatal dopamine transporter would participate in the response of PMDD and in patients with bipolar disorders (BD). The only neurotrophic factor associated with ECT response was vascular endothelial growth factor. In BD, some oxidative stress metabolites had a clinical correlation, while tryptophan metabolism showed a clinical association in BD and PMDD. Furthermore, in PMDD, some neurodegeneration markers were implicated in the MA of ECT. There were no other biological dimensions associated with BD. In PMDD, multiple inflammatory mediators were associated with the clinical response (natural killer cells, tumor necrosis and growth factors, and interleukins 1, 4, 6, 10,1β). Likewise, some structures and circuits consistently involved at the morphological and functional level are the default mode network, cognitive control networks, frontal, temporal, cingulate, occipital and temporal cortices, frontal, temporal, precentral, fusiform and left angular gyri, hippocampus, thalamus and amygdala. Investigations are mostly focused on PMDD, are observational, and their samples limited, but they show relatively consistent results with clinical significance.