Transcranial stimulation protocols, particularly transcranial direct current stimulation (tDCS), are attracting increasing interest both for neuroscientific study and as putative therapies for a wide range of neurological and psychiatric disorders. However, before the potential of this technique can be fully utilized, the physiological effects it induces must be understood. This chapter reviews the current knowledge of the physiological mechanisms through which tDCS exerts its effects, both during stimulation and in the after-stimulation period. The techniques by which these effects may be quantified are also reviewed. The chapter concludes with a discussion of the evidence concerning the relationship between physiological changes induced by tDCS and those underpinning endogenous plasticity.