This review by Charlotte J. Stagg and Michael A. Nitsche explores the physiological basis of transcranial direct current stimulation (tDCS), a noninvasive technique that induces excitability changes in the stimulated cortex. The authors discuss the growing interest in tDCS for treating various neurological and psychiatric disorders, supported by clinical trials and detailed pharmacological, neurophysiological, and imaging studies. They highlight the role of synaptic plasticity, particularly long-term potentiation (LTP) and long-term depression (LTD), in mediating the effects of tDCS. The review also examines the mechanisms by which tDCS affects motor learning, proposing a theoretical framework that links tDCS-induced changes in membrane potential and synaptic plasticity. Additionally, the authors discuss the safety and efficacy of tDCS, emphasizing its potential to induce long-lasting behavioral changes through modulation of synaptic strength. The review concludes by suggesting that further research is needed to fully understand the cellular mechanisms underlying tDCS's effects and to optimize its clinical applications.This review by Charlotte J. Stagg and Michael A. Nitsche explores the physiological basis of transcranial direct current stimulation (tDCS), a noninvasive technique that induces excitability changes in the stimulated cortex. The authors discuss the growing interest in tDCS for treating various neurological and psychiatric disorders, supported by clinical trials and detailed pharmacological, neurophysiological, and imaging studies. They highlight the role of synaptic plasticity, particularly long-term potentiation (LTP) and long-term depression (LTD), in mediating the effects of tDCS. The review also examines the mechanisms by which tDCS affects motor learning, proposing a theoretical framework that links tDCS-induced changes in membrane potential and synaptic plasticity. Additionally, the authors discuss the safety and efficacy of tDCS, emphasizing its potential to induce long-lasting behavioral changes through modulation of synaptic strength. The review concludes by suggesting that further research is needed to fully understand the cellular mechanisms underlying tDCS's effects and to optimize its clinical applications.