In recent years, numerous alternatives to VKAs have been developed, the first competitors to warfarin are the novel oral anticoagulants (NOAC) or better referred to as Direct Oral Anti-Coagulant (DOAC) or Target Specific Oral Anti-coagulant (TSOAC): These drugs have definite advantages and disadvantages that should be clear to the physicians before prescribing any of them for patients. Many clinical trials, which involved thousands of patients provided definite information about the efficacy and the safety of DOACs, yet, many physicians remain reluctant to prescribe these drugs due to lack of answers to real world questions. The concerns are directed towards appropriate patient selection (The choice should be made according to age, renal function, compliance, cost, clinical condition, intake of other drugs), the mechanism of switching between agents. How to manage regarding any procedural measurement? How these drugs affect routine laboratory tests and when do we need monitoring? Knowledge of other drugs that interact with the DOAC and management of severe bleeding will be reviewed and recommendations will be given to all these concerns.