Chronic wasting disease (CWD) is perhaps the most problematic prion disease at present, considering its rapid spread in North America, its presence in both captive and wild animals, and its unknown zoonotic potential. Although several strategies have been attempted to contain the spread of CWD, their success appears to be limited. One of the main problems associated with the management of this disease lies in its diagnosis. At present, CWD diagnosis is evaluated using post-mortem tissues using techniques of insufficient analytical sensitivity. As a consequence, these techniques do not allow for the identification of infected animals using biological samples that could be collected from live subjects. Along this line, further development of prion amplification methods may fill this much-needed gap. This chapter summarizes the current methods used to diagnose CWD in regulatory and laboratory settings, and provides perspectives on how new technologies may help facilitate the identification of diseased animals.