Hippocampal sclerosis (HS) is characterized by a severe loss of neurons and gliosis in the CA 1 sector of hippocampus. HS was found in several post mortem series of demented patients either in association with specific pathologies, such as Alzheimer disease (AD) or isolated. The symptomatology and etiology of HS remain unclear, but, in the cases of pure HS, the usual clinical diagnosis was AD. It is suggested that HS could explain unusual association of an amnestic syndrome with fronto-temporal dementia or dementia with Lewy bodies. Moreover, it could also be responsible of amnestic disorders similar to those found in AD, but remaining isolated during many years. Epilepsy or anoxia, the main causes of HS, are rarely found in the history of demented people with HS. Therefore, HS might be due to a degenerative process close to dementias lacking histologic features. Diagnosis of HS can be made during life using MRI, specially high resolution MRI or fast-spin echo relaxation time.