Scrapie is a slowly developing transmissible spongiform encephalopathy (TSE) occurring naturally in sheep and goats. At present, there is no efficient antemortem diagnostic test for TSEs. Electroencephalograms (EEGs), electrocardiograms (ECGs), magnetic-resonance imaging (MRI), positron emission tomography (PET), single photo emission computed tomography (SPECT), as well as conformation-dependent immunoassay (CDI), which show patterns characteristic of prion diseases, can obtain diagnostic information for TSEs. Other methods include testing cerebrospinal fluid for the presence of 14-3-3 proteins, Fourier transformation infrared spectroscopy (FTIR), brain biopsy, nasal biopsy and tonsil biopsy. For better TSE diagnosis, most TSEs need to be confirmed by the presentation of abnormal prion protein by Western blot, ELISA immunochemical methods, or immunocytochemistry methods, or by bioassays, a more sensitive but time-consuming method, which involves inoculating suspended homogenates into susceptible hosts and waiting for a long incubation period to conclude. An antemortem diagnostic test for TSEs can be done from spleen or lymph node biopsy by evaluating PrPSc presence. Since it has been suggested that the buffy coat of TSE animals may carry infectivity, a method for presymptomatic diagnosis of TSE from blood is clearly possible and desirable. At present, antibodies against prion protein cannot distinguish normal prion protein (PrP C) and abnormal prion protein (PrPSc); there is no reliable antibody to detect PrPSc only. In this review, we propose that the development of gene chips and / or protein chips for assays of TSE diseases might prove very useful. A great deal of basic research on TSE diagnosis, prevention, and treatment remains to be conducted.