Human prion disease is a rare, uniformly fatal neurodegenerative disorder.Its precise pathogenesis is obscure. The clinical profile of the disease differs among its various forms. There are no definitive diagnostic tests (except for brain biopsy) or proven treatment. To increase the clinical diagnostic sensitivity and specificity, three laboratory tests, including electroencephalogram, cerebrospinal fluid testing for 14-3-3 protein, and magnetic resonance imaging, are currently used. Additionally, proton magnetic resonance spectroscopy, positron emission tomography and single photon emission computed tomography can provide interesting and novel results in the research of human prion disease.