This article considers the evidence underpinning the UK Health Department's guidance that root canal instruments must be treated as single use as a precaution to reduce any risk of variant Creutzfeldt- Jakob disease (vCJD) transmission. Although there have been fewer than 170 clinical cases of vCJD in the UK to date, there is concern that an unknown number of the population may carry vCJD infection without showing symptoms. This creates the potential for secondary (person-to-person) transmission, as has happened via blood transfusion. There is currently no evidence of vCJD having been spread by dentistry, but animal models suggest that this may be possible. In particular, evidence presented by the Health Protection Agency (HPA) from a bioassay study has indicated that murine oral tissues, for example dental pulp, can harbour prion infectivity. It is possible that dental/oral tissues of humans infected with vCJD could also carry infection. If so, residual protein adhering to dental instruments may transmit vCJD infection to other patients. Decontamination would reduce this risk, but a number of clinical studies have shown that the decontamination methods used in dentistry would not eliminate the risk entirely. Furthermore the large number of dental procedures carried out each year means that even small transmission risks per procedure could create an appreciable risk to public health. Given that there are many uncertainties, including the infectivity of relevant tissues in those incubating the disease, the typical effectiveness of instrument decontamination, and the current prevalence of subclinical infection, a precautionary approach is warranted. Specifically, this article supports the decision that root canal instruments must be treated as single use, as well as promoting further initiatives to improve the effectiveness of decontamination for the generality of dental instruments. Keywords: Creutzfeldt-Jakob disease, cross-infection, endodontic files, prions, residual protein