Direct oral anticoagulants have recently emerged as an attractive choice for patients requiring anticoagulation treatment. They have a rapid onset of action and can be administered at fixed doses without the need for routine anticoagulation monitoring. They may present fewer interactions than warfarin but further experience is needed to assess the clinical significance of the interactions with cytochrome CYP3A and P-gp inhibitors/inducers. A higher rate of bleeding has been observed in association with antiplatelet agents or non-steroidal anti-inflammatory drugs. Their safety profile has not been sufficiently studied in the elderly, and in patients with liver disease or severe renal impairment. Dose adjustment is necessary in patients with moderate renal impairment and a higher bleeding rate has been observed in this subgroup, although not higher than with warfarin. The clinical settings that require monitoring of coagulation assays have not yet been specified. Reversal of their anticoagulant effect may be problematic in case of severe bleeding. Therefore, despite the obvious advantages of the direct oral anticoagulants, experience is still lacking for many patient subgroups in which they should be withheld awaiting more data.