Chronic wasting disease (CWD), a fatal transmissible spongiform encephalopathy of deer (Odocoileus spp.) and elk (Cervus elaphus), presents a challenge to wildlife managers because little is known about its transmission, yet it could severely threaten wildlife populations if action is not taken rapidly. Published mathematical models predict that CWD could devastate populations of free-living deer and elk, prompting wildlife managers to attempt large-scale eradication of deer in hopes of containing CWD outbreaks. Our objective is to critically examine the theoretical and empirical support for current models of CWD epizootiology, in light of herd health-management actions. We identify a critical, untested premise (i.e., strictly frequency-dependent transmission) that underlies the dire model predictions. We re-evaluate published comparisons of model output with field data and find little support for published model structures. Given the uncertainty surrounding the future effects of chronic wasting disease on deer and elk populations, and the potential costs of unnecessarily culling large numbers of charismatic and valuable animals, we propose that consideration of alternative models and management actions in a decision–theoretic framework is necessary for wildlife management actions to retain their scientific basis.