Atrial fibrillation is a commonly encountered arrhythmia associated with increased risk for thromboembolic events. Anticoagulation is necessary to decrease the risk of ischemic stroke. Traditionally, warfarin has been the only oral pharmacotherapeutic option for long-term anticoagulation in patients with nonvalvular atrial fibrillation (NVAF). Recently, non-vitamin K antagonist oral anticoagulants (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban, have become available as alternatives for warfarin in the prevention of stroke in patients with NVAF. Recently published atrial fibrillation guidelines contain new recommendations for risk stratification tools in determining the need for anticoagulant therapy and incorporate NOAC pharmacotherapy options for stroke prevention in patients with NVAF. NOACs offer several advantages over warfarin, including the elimination of routine laboratory monitoring, fewer drug and food interactions, and rapid therapeutic onset and offset. However, the lack of antidote in the case of serious bleeding and lack of data for long-term use in patient populations at risk for bleeding is problematic. Older adults are at high risk for thromboembolic and bleeding events as a result of anticoagulation and require special consideration when selecting anticoagulant therapy. The risk of drug accumulation and bleeding is concerning in the presence of renal impairment. The objective of this review is to provide the clinician with an update on the use of NOACs for NVAF, focusing on older adults and patients with renal impairment in light of recently published atrial fibrillation guidelines. Available data on using NOACs in coronary artery stenting, cardioversion, and ablation are also reviewed.