Deep Brain Stimulation (DBS) is a well-known procedure for the treatment of a wide range of neuropsychiatric disorders, comprising advanced Parkinson’s Disease (PD), Dystonias, Alzheimer’s Disease (AD) and Dementias, as well as drug-resistant major depressive disorder and Schizophrenia. A number of anatomical targets have been proposed, strictly depending on the underlying disease and its clinical features. Moreover, novel biomarkers have been recently identified, as the subthalamic (STN) beta oscillations in PD, possibly guiding new adaptive (closed-loop) devices. Nonetheless, whether DBS may exert a neuroprotective and disease-modifying effect, rather than being a purely symptomatic treatment, is still a matter of debate. Pre-clinical data in animals have recently shown that DBS may prevent both the lateral ventricle enlargement and the mal-development of serotoninergic and noradrenergic transmission in psychotic disorders. In AD, studies in rodents have proved that increase of cholinergic neurotransmitters, hippocampal neurogenesis and reduction of amyloid plaques are associated with DBS. Also for non-invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS), a growing body of the literature has recently shown a “neuroprotective” effect, regarding both in vivo and in vitro models. The demonstration of a neuroprotective effect is of key importance for the patients’ selection, as well as for the choice of anatomical targets, and may help to identify novel electrophysiological markers to guide invasive and non-invasive approaches.