Electroconvulsive therapy (ECT) is one of the most effective methods for managing treatment-resistant depression. Although the proposed mechanisms of action have thus far mainly been investigated at the cellular level, recent observations and developments in the field of molecular biology and genomics have provided novel insights in the actual molecular underpinnings of dynamic alterations in gene expression, particularly in response to environmental exposures, and experience-dependent plasticity, both of which are highly relevant to ECT. Here, we provided a brief background on epigenetics and we reviewed the current state of knowledge on epigenetic mediation of ECT-related therapeutic effects. We performed a systematic search on the effects of ECT on epigenetics and found only a limited number on animal studies relevant to our search. These studies, however, support the notion of a robust impact of ECT on epigenetic mechanisms and set the stage for human ECT studies on the epigenetic machinery.