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While electrical stimulation of brain tissue has been thoroughly investigated over the last decades, ongoing questions remain regarding the neurophysiological effects of low-level electric fields (on the order of 1 V/m) on brain activity. Electric fields at such levels are, for example, induced by transcranial direct/alternating current stimulation (tDCS/tACS). Action potentials can be indeed elicited when applied (supra-threshold) electric fields are in the 10–100 V/m range, while lower (sub-threshold) electric fields result in more limited and subtler membrane polarization effects. In this review, we address the question of the mechanisms underlying the immediate effects (also referred to as acute, concurrent or short-term) and the lasting effects (also referred to as long-term or after-effects) of low-level electric fields on brain tissue. We review recent evidence at the in vitroand in vivo(animal and human) level, and also present mechanistic insights gained from in silicomodels, which are still few but have received increased attention over the recent past years. We highlight the convergent evidence towards potential mechanisms, and also discuss discrepancies between in vitrostudies and human tDCS/tACS studies that require further investigation to bridge the gap between the single-cell and large-scale network level. Possible novel avenues of research are discussed.