This chapter discusses the rationale and methodology for applying techniques of active and passive neuromodulation for treatment-refractory post-traumatic stress disorder (PTSD). Neuromodulation derives from the concept of neuroplasticity, which signifies long-term changes in the effectiveness of connections between distinct parts of the central nervous system. These changes are reflected across multiple levels of the nervous system, going from the cellular level to circuits and large-scale brain networks. It has been long suggested that altered neuroplasticity is a biomarker of neuropsychiatric diseases. With recent advances in neuroscience, research is emerging on evaluating the potential of modulating neural circuits by using innovative technologies, including noninvasive and invasive brain stimulation, EEG-neurofeedback, and fMRI neurofeedback.