Non-invasive brain stimulation methods, such as Transcranial Magnetic Stimulation (TMS), are widely used worldwide to make causality-based inferences about brain-behavior interactions. TMS-based clinical applications have been shown promising to treat neurological or psychiatric diseases. TMS works by inducing non-invasively electric currents in localized cortical regions thus modulating their excitability levels and ongoing activity patterns depending on stimulation settings: frequency, number of pulses, train duration and intertrain intervals. Proper use of TMS in the fundamental and clinical neuroscience research requires a deep understanding of its operational principles, risks, potential and limitations. In this article we present the principles through which TMS is thought to operate. Readers will be provided with the bases to be able to understand and critically discuss TMS studies and design hypothesis driven TMS applications for basic and clinical neuroscience. Moreover, some recently identified physiological phenomena which that can dramatically influence the efficacy and magnitude of TMS impact and technological and methodological developments to guide TMS interventions that are becoming mainstream in the field will be also reviewed.