tDCS appears to be a promising tool in neuroplasticity research with some perspectives in clinical neurophysiology. It is closely related to modulation of cortical excitability and activity which are key mechanisms for modulating neuroplasticity. Long-term potentiation and long-term depression-like effects have been shown to be involved in learning processes in animal studies so far. Stimulation with weak direct currents is capable of inducing stimulation-polarity-dependent, prolonged, diminutions or elevations of cortical activity and excitability, most probably elicited by a hyper- or depolarisation of resting membrane potentials. Moreover, these modulations are functionally important, since they affect learning processes and epileptic activity. Here excitability changes have been accomplished in the human by non-invasive transcranial direct current stimulation (tDCS). They share some important features with these well-known neuroplastic changes: The duration of the effects depends on stimulation duration and intensity, they are of intracortical origin, and the prolonged effects depend on NMDA-receptor activity. Thus, this technique is a promising method in the field of neuroplastic research in animals and humans and could evolve as a therapeutic tool in some neuro-psychiatric disorders which benefit from modulation of cortical excitability.