Novel oral anticoagulants, direct thrombin inhibitors, and factor Xa inhibitors are being introduced into clinical practice. In contrast to vitamin K antagonists, such as warfarin, these novel agents, because of their relatively wide therapeutic range and predictable pharmacokinetics, have been evaluated in clinical trials and approved for clinical use without the need for routine coagulation monitoring. On occasion, it will be important to assess the anticoagulant status of patients treated with these agents. As a result of their targeted mechanisms of action, they affect standard coagulation assays differently than vitamin K antagonists and heparins, and such assay results may not provide clinically useful information. Thus, less commonly used coagulation assays (eg, chromogenic anti-factor Xa activity assays, diluted thrombin time, and ecarin-based clotting tests) may be introduced into clinical practice. These assays are currently limited by the absence of validated therapeutic targets and lack of standardization across laboratories, vendors, and medication classes. This article provides an overview of the coagulation assays and their potential role in determining the anticoagulant status of patients treated with the emerging anticoagulants.