In 1838, Deschambre coined the term “lacune” to describe small cavities caused by the resorption of small deep brain infarcts. Durand-Fardel noted that some small cerebral cavities contained a small blood vessel and were not infarcts but enlarged perivascular spaces. He introduced the term état criblé to describe multiple enlarged perivascular spaces. Subsequent authors often called any small hole in the brain a “lacune” and failed to distinguish between lacunar infarcts and enlarged perivascular spaces. In 1901, Pierre Marie made a distinction between lacunar infarcts, état cribilé, and état porose (cerebral porosis), holes in the brain caused by postmortem gas formation. He established the morphological characteristics and the common association of lacunes with isolated hemiplegia (Pullicino et al 1993). He called multiple lacunar infarcts état lacunaire, a term that is now also referred to as the “lacunar state." Marie did not fully understand the pathogenesis of lacunar infarcts and thought that some were due to an inflammatory process, “vaginalite destructive." In 1960, Charles Miller Fisher stressed the major role of arterial hypertension and intracranial atherosclerosis in the pathogenesis of lacunes and redefined lacunes as “small, deep cerebral infarcts” due to occlusion of a single perforating vessel (Fisher 1965; 1969). He coined the term “lipohyalinosis” for the segmental arterial pathology that affects small penetrating arteries and causes lacunar infarcts. He also showed that atherosclerosis of the origins of penetrating arteries, “microatheroma,” is a frequent cause of lacunar infarcts.