Millions of patients in the United States are currently prescribed some form of anticoagulation therapy. Recently, novel oral anticoagulants (NOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, have begun to replace warfarin as the drugs of choice for anticoagulation. As the use of these medications becomes more widespread, it is increasingly important for gastroenterologists to understand the risks associated with performing endoscopic procedures on patients who are taking NOACs. In this review, we provide an overview of the NOACs and current guidelines from international societies regarding the management of patients scheduled to undergo endoscopic procedures who are prescribed these medications. Finally, we offer a perspective on future studies required to adequately investigate and characterize the effects that these drugs have on a patient’s risk for bleeding in the peri- and/or postprocedural timeframes.