Piracetam was originally developed as a cyclic derivative of gamma-aminobutyric acid (GABA) to treat anxiety. While it failed as an anxiolytic, it showed considerable efficacy in tests of “central nystagmus” as a model of vertigo, which at that time was only seen for antihistaminic and anticholinergic compounds. Piracetam not only did not have antihistaminic or anticholinergic properties, but even did not show any central activity like sedation, stimulation, or influence on autonomic function. However, as a rather new spectrum of pharmacological properties piracetam did facilitate interhemispheric transfer, enhanced the cerebral resistance to noxious stimuli like hypoxia and, most importantly, it enhanced or facilitated learning and other cognitive functions (Giurgea, 1982). These cognition improving properties still represent the basis of the present therapeutical use of piracetam in many countries all over the world in the whole spectrum of geriatric memory disorders, in cases of impaired cognitive functions after head injuries, and also in vertigo. Even if piracetam can facilitate learning and other cognitive functions under normal conditions (e.g., young healthy volunteers), it has been a most consistent observation over nearly three decades of piracetam's clinical use that the cognition improving properties are much more pronounced when brain function is impaired such as aging, hypoxia, cerebral injuries, or Aß load in AD, conditions which all have mitochondrial dysfunction as common final pathway. Since these preclinical and clinical data form the link between mitochondrial protection as major preclinical mechanism of action and the clinical efficacy of piracetam in a large variety of diverse groups of older subjects with cognitive impairment, some of these data will be reviewed shortly.