Deep brain stimulation (DBS) has been applied widely in clinic to treat movement disorders such as Parkinson’s disease. It also shows great prospects in the treatments of intractable epilepsy, refractory obsessive-compulsive disorder, and other diseases of the central nervous system in brain. Over the past three decades, the mechanisms of DBS have emerged gradually based on multiple lines of evidence in clinical applications, in animal experiments, and in simulations of computational models. Important advances in DBS mechanisms have been achieved although final conclusions are still under debate. This review analyzes and summarizes the development of DBS theories from electrophysiological perspectives: from the original theory of inhibitions or excitations to the recent prevalent theory of modulations; from focusing on neuronal activity locally at stimulation sites to discovering the decoupling of somatic and axonal responses, and further to discovering the intermittent depolarization block of axons induced by high frequency stimulations, together with de-synchronous activity presumably caused by axonal activity in population neurons in the projection brain regions. The series of advances indicate that DBS has complex mechanisms in modulating the neuronal networks. Understanding the mechanisms of DBS has significance for improving DBS therapies, for developing new stimulation modes, and for extending its clinical applications.