The twenty-first century is a time of increased uncertainty over the future of sites associated with the Holocaust. As “sites of memory” and “sites of conscience,” they are part of an ongoing debate as to their contentious place within international heritage conventions (UNESCO 2023). Further, while much attention has been paid to the specific challenges of managing Holocaust heritage in the context of the imminent passing of the last of the Holocaust survivors (Pearce 2020; Gilmore and Magee 2018), and the rise in Holocaust denial and distortion (Bauer 2020), the challenges posed by anthropogenic climate change raise yet more uncertainties. Holocaust heritage—along with other heritage places—faces accelerated decay and destruction brought on by the climate emergency, including extreme weather events. Across Europe, examples include the former camp of Fossoli (Italy), already fragile following an earthquake; the collapse of a wall at the former camp of Sachsenhausen (Germany); and the ongoing ruin of the Dresden Barracks in the former ghetto of Terezin (Czech Republic), after a series of storms. Other sites are threatened by rising sea levels—for example, the mass graves and former cemetery in Alderney in the Channel Islands. However, the usual options in the face of destruction of the historical record, which include either expensive preservation and restoration programs or a form of “curated decay” (DeSilvey 2017), are particularly problematic given the complexities of Holocaust sites because of the specific histories and stakeholders. While preservation and restoration are often beyond the financial reach of most Holocaust sites, “curated decay” raises questions about the retention of historic fabric which, as well as being protected under various forms of heritage legislation, is understood as part of the evidence of genocide. Therefore, the concurrent anxieties over the passing of the survivor generation, the rise of Holocaust denial and distortion, and the challenges of climate change create uncertainties for heritage professionals and site managers as to how to best manage the safeguarding of these unique sites. Using the former camp at Fossoli in Italy and the former ghetto of Terezin as case studies, this paper critically examines ideas of loss and uncertainty within heritage practice to explore the lessons for safeguarding Holocaust heritage in the Anthropocene.