<b><i>Background/Aims/Methods:</i></b> Electroconvulsive therapy (ECT) is still one of the most potent treatments in the acute phase of major depressive disorder (MDD) and particularly applied in patients considered treatment resistant. However, despite the frequent and widespread use of ECT for &#x3e;70 years, the exact neurobiological mechanisms underlying its efficacy remain unclear. The present review aims to describe differential antidepressant and cognitive effects of ECT as well as effects on markers of neural activity and connectivity, neurochemistry, and inflammation that might underlie the treatment response and remission. <b><i>Results:</i></b> Region- specific changes in brain function and volume along with changes in concentrations of neurotransmitters and neuroinflammatory cytokines might serve as potential biomarkers for ECT outcomes. <b><i>Conclusions:</i></b> However, as current data is not consistent, future longitudinal investigations should combine modalities such as MRI, MR spectroscopy, and peripheral physiological measures to gain a deeper insight into interconnected time- and modality-specific changes in response to ECT.