Publisher Summary The transcranial direct current stimulation (tDCS) is a technique of brain stimulation that is increasingly investigated as a clinical tool for the treatment of neuropsychiatric disorders. The growing interest in this technique underscores the importance of elucidating its underlying neurophysiology. Studies from electrophysiology and transcranial magnetic stimulation have shown that tDCS can modulate cortical- excitability in a polarity-dependent fashion. tDCS is shown to modulate activity in both the motor and visual cortices, and more recently is shown to directly influence excitability of the spinal cord. Anodal tDCS is shown to increase intracortical facilitation and diminish intracortical inhibition, while cathodal tDCS is shown to have the reverse effect. tDCS is also shown to modulate transcallosal inhibition and may be a promising tool for enhancing the effects of paired-associative stimulation. Neuropharmacological studies suggest that the immediate effects of tDCS are due to modulation of neuronal membrane potentials at subthreshold levels, thus increasing or decreasing the rate of action potential firing.