Direct current (DC) is very effective in modulating spontaneous neuronal firing. The history of electrophysiology starts with the discovery of the biological effects of DC and as early as two centuries ago scalp DC was used to treat mental disorder. Psychophysiological investigations suggested a possible effect of scalp DC in humans. More recently several studies assessed, with motor potentials evoked by transcranial brain stimulation, the motor-cortical excitability changes induced by scalp DC. Even weak DCs pass through the scalp and influence human brain activity. DCs delivered at relatively strong intensities (1 mA) and for long periods (10 min or so), not only influence (either increase or decrease) brain excitability during their application in normal subjects, but induce persistent changes in excitability after their offset that, at least in the motor cortex, can last for almost 1 h. Scalp DC might represent a non-invasive simple and valuable potential treatment for psychiatric and neurologic diseases with changes in brain excitability or focally abnormal (increased or decreased) function.