In the proposed new European chemicals regulations—the REACH system—the improved control of persistent and bioaccumulating substances is stated as one of the tasks being of particular importance. In this article, the reliability and validity of the scientific basis for identification of persistent (P), bioaccumulating (B), and toxic (T) substances, and for assessing the risks that these substances may pose, are discussed. We have used the European Union risk assessment of pentabromodiphenyl ether, PentaBDE (CAS 32534-81-9) as a study case in the analysis. It is concluded that for PBT substances there is room for development both with regard to test methodology and with regard to risk assessment procedures.