Wernicke’s Encephalopathy (WE) is an underdiagnosed, potentially fatal, acute or subacute neurologic disorder caused by the impairment of thiamine (vitamin B1) -dependent enzymatic activity in susceptible brain cells. The biologically active form of thiamine (TH), thiamine diphosphate (THDP), serves as a cofactor for several apoenzymes involved mainly in the carbohydrate metabolism. Except for very rare cases, WE occurs in the presence of TH deficiency, which is directly related to at least two other clinical entities: neurological beriberi and cardiovascular beriberi. The preferential expression of one (or more) of these entities may be the consequence of genetic polymorphism of genes encoding TH transporters. The topography of WE brain lesions is highly specific, typically the periventricular and periaqueductal grey areas being symmetrically involved. In the majority of cases the early so-called ‘biochemical lesions’ are completely reversed if TH is promptly supplied. However, if the THDP dependent enzymatic activity is not restored, irreversible structural damage and eventually exitus may occur (Donnino, Vega et al. 2007; Hazell and Butterworth 2009; Thorarinsson, Olafsson et al. 2011).