Prion disease is the new designation of a group of spongiform encephalopathies, all invariably fatal, which show similar clinical and neuropathological changes. They comprise a range of distinct diseases in both animals and man, and spontaneous, hereditary and transmissible forms are recognized. Until the sudden occurrence in the mid-1980s of an epizootic of a formerly unknown disease, popularly named ‘mad cow disease’, in cattle in the UK, very little attention had been paid to these rather obscure diseases. Concurrently it was asserted that the disease-causing agent appeared to be a ubiquitous mammalian brain constituent, and the disease mechanism a conformational change of its structure. These events have not only led to a new understanding of these extraordinary diseases, but have also provided insight into both neurodegeneration and disease mechanisms at the molecular level. Moreover, in 1997 the prion concept earned its originator the second Nobel price for medicine within this scientific field. In this introduction and overview of prion diseases, historical and philosophical perspectives are presented along with descriptions of the diseases in both animals and man. Epidemiology, genetics and transmissibility are also covered.