Fronto-temporal dementia is the commonest clinical manifestation of fronto-temporal lobar atrophy. It is associated with three types of underlying histology: microvacuolation or spongiosus (frontal lobe degeneration type), gliosis with or without inclusion bodies and swollen neurones (Pick-type), and motor neurone disease type. The clinical disorder presents in the presenium, is highly familial and is characterized by profound personality change, social incompetence and stereotypic ritualistic behavior. Language becomes attenuated, culminating in total mutism. Visuo-spatial skills are strikingly preserved. The electroencephalogram is normal and structural and functional imaging reflect fronto-temporal lobar atrophy. In a minority of cases the amyotrophic form of motor neurone disease coexists with fronto-temporal dementia and has a rapid and brief duration of illness. Phenotypic characterization of patients at each level of description: clinical, anatomical, and histological, provides a foundation for the molecular genetic studies which ought to shed light on the etiology of this form of focal cerebral degeneration.