The detection of carbapenem-resistant organisms (CROs) represents a substantial challenge for many clinical laboratories. In this review, several phenotypic and non-phenotypic methods for detecting CROs are discussed. However, no consensus has yet been reached with regards to the single most optimal method. Due to differences in carbapenem-resistant activity between carbapenemases, the simultaneous use of 2 or more phenotypic detection methods can improve the detection of CROs compared with a single technique. Molecular methods are currently favored because the majority can be performed rapidly with a high level of accuracy. Whole-genome sequencing (WGS) yields unambiguous data pertaining to complete analysis of the entire genome and may ultimately become a highly powerful tool in routine clinical settings. However, WGS is still relatively expensive and requires an automated data interpretation system. The routine implementation of this technique in clinical laboratories may not occur for several years, particularly in developing countries.