Chronic wasting disease (CWD) is the most transmissible of the prion diseases. In 2016, an unexpected case was found in Norway, the first in Europe. Since then, there have been 32 confirmed cases in Norway, Sweden, and Finland. This paper aims to examine the situation from a social and political perspective: considering the management of CWD in the Swedish part of Sápmi—the Sami ancestral land; identifying the place of the Sami people in the risk management–because of the threats to Sami reindeer herding that CWD presents; and understanding how the disease can modify the modalities of Indigenous reindeer husbandry, whether or not CWD is epizootic. Based on interviews with various stakeholders and by examining the social sciences literature, this paper shows that the health risk management is structured by a politico-scientific controversy about the recognition, or not, of atypical and classical CWD. The Sami herders are currently cooperating with the state authorities in the surveillance program to sample their herds. This involvement takes place in a situation where the balance of power between the Sami people and the state, or the European Union, is framed by its colonial context. This has consequences with respect to the definition of a common interest and to implementing sanitary measures. The particular features of reindeer herding are seen as a challenge to managing CWD risk, compared with European health standards. We argue that CWD will greatly modify the modalities of Indigenous reindeer herding, whether there are positive cases or not in the Sami reindeer. By implementing new health guidelines, the authorities will create a cascading effect in Sami land and its use. The CWD situation in Fennoscandia is full of uncertainty but may cause a major shift in the organization and the governance of Sápmi. In September 2020, the identification of a new CWD case in a wild reindeer in Norway started a new episode in the disease management in Fennoscandia. Our paper raises various questions linked to understanding this new step in this crisis which is not only epidemiological, but also socio-cultural and political.