The aim of this chapter is to review the current significance of motor cortex stimulation (MCS) for either chronic neuropathic pain or non-painful conditions. The epi- or subdural lead implantation over the central sulcus or precentral gyrus is performed in selected patients if conservative treatments, pharmacological therapies and multimodal settings are ineffective. Initial case series with post-stroke pain or trigeminal neuropathic pain were published in the early 1990s. To date more than 700 cases and about 75 prospective or retrospective clinical trials, patient samples or reviews are published. The exact mode of action is unknown but functional studies using magnetic resonance imaging (MRI) or single-photon emission computed tomography (SPECT) reveal a certain modulation of pain-related subcortical areas like the thalamus, cingulate gyrus, etc. via corticothalamic and other connections. The focus of this chapter is to highlight the clinical practical aspects of patient selection and performance of the procedure as an individual and therefore experimental treatment option. At the moment, all implanted materials are used off-label because there is no approval for this specific indication. The current evidence of these invasive procedures for different diagnoses is presented.