The potential existence of clinically silent cases of bovine spongiform encephalopathy (BSE) among cattle and of humans incubating the new variant Creutzfeldt-Jakob disease (nvCJD) are still a major public health concern. Therefore, the development of screening tests for transmissible subacute spongiform encephalopathies (TSSE) in man and animals remains a priority. In the first part of this paper, we review the main methods used to diagnose clinical TSSE, such as brain imaging, electroencephalogram (EEG) analysis and cerebrospinal fluid (CSF) analysis. In the second part, we present the postmortem tests used to confirm a TSSE diagnosis, such as inoculation of laboratory animals, histological examination and identification of abnormal prion protein (PrPres) using biochemical methods. Finally, the third part presents the rapid tests used in Europe such as Prionics, Bio-rad and Enfer, validated by the European Commission (EC) for post-slaughter BSE diagnosis in cattle. However, it is too early to predict the use of these new techniques in the field.