Abstract: Non-invasive brain stimulation techniques (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electric stimulation (tES), are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders, albeit with varying success. The rationale behind the use of NIBS has historically been that stimulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes. However, over the past decade, there has been a marked increase in our understanding of the neurobiological mechanisms of NIBS, in particular for rTMS. The increasing breadth of research in humans and animal models has resulted in a more nuanced understanding of how NIBS affects the brain with the hope for improved therapeutic applications. In this perspective we summarize some of the newly identified mechanisms contributing to NIBS effects, focusing on rTMS, and propose how emerging experimental techniques could be leveraged to further understand and optimize non-invasive brain stimulation.