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Over the past 9 years, the pharmacologic approach to stroke prevention in atrial fibrillation (AF) has been revolutionized by the introduction of four direct oral anticoagulants (DOACs) in clinical practice. Their use is supported by the results of phase III randomized controlled trials (RCTs) and by more recent real world studies. Given that there is no RCT ongoing or planned on the direct comparison of different DOACs, the clinician is left with the responsibility to choose among dabigatran, rivaroxaban, apixaban or edoxaban. In this article, we will review DOACs’ pharmacokinetic and pharmacodynamic properties, data supporting their use in AF cardioversion, the general effectiveness and safety of these drugs and the use of reduced doses, in an attempt to give the clinician a vademecum of evidence supporting the practical use of single DOACs.