The pathophysiological mechanisms underlying normal aging and neurodegenerative disorders represent the focus of a bulk of recent research. Physiological brain aging is characterized by a progressive dysfunction and loss of synaptic contacts and neuronal abnormal apoptosis. Neural and synaptic redundancy as well as functional and structural plastic remodeling of brain networking promote maintenance of brain activity in healthy elderly for everyday life but are not sufficient to face the pathologic scenario of excessive synaptic/ neuronal loss as in dementias. It is, then, important to implement techniques that are able to measure changes in normal aging brain and to discriminate the threshold from neurodegenerative processes. Rhythmic electromagnetic brain oscillatory activity is a hallmark of neuronal function and it contains relevant traces of neuronal assemblies cooperation across different brain functions; an integrated approach utilizing modern neurophysiological techniques, including electroencephalography (EEG), event-related potentials (ERPs), and transcranial magnetic stimulation (TMS), together with biological markers and structural and functional imaging is promising for largescale, affordable, and non-invasive intercept of at-risk populations both at a group and probably also at a single-subject level. This approach might also guarantee the possibility of studying drug-induced changes in the electrical properties of the human cortex, developing and testing models of brain connectivity and treating neuropsychiatric diseases. In this paper some neurophysiological cutting-edge techniques will be presented that provide innovative information and deal with the broad issue of the role of neurophysiology for the assessment of patho-physiological aging and dementia also providing new insight to the actions of central nervous system drugs at the cortical level.