Chronic wasting disease (CWD) is a prion disease of cervids such as deer and elk in North America. Unlike other transmissible spongiform encephalopathy (TSE) such as scrapie, CWD occurs in both captive and wild ranging animals, but not in domestic ruminants such as sheep and cattle. In this paper, the history of the disease, pathogenesis of CWD, susceptibility of animals, its transmission mechanisms, potential origins of the disease, diagnostic methods in the field and laboratory tests, surveillance and survey systems in the USA and Canada, control strategies, economic impact of the disease, food and feed safety, and the risks in human and animals are reviewed and summarized. Although there is no evidence that CWD has been transmitted to humans, it may have the potential to infect humans.