The search for the ideal anticoagulant has been one of the most active research fields in medicine in the past few years. Anti-vitamin K replacement, particularly in the long term treatment of venous thromboembolism is a difficult objective to achieve due to the wide experience gathered in normal practice and low costs. But to improve the weak points of these drugs is an attractive challenge and would have a great health and social impact. It can be seen that the low molecular weight heparins, or even pentasaccharide, drugs that are already available on the market, although the have very predictable pharmacokinetics, their parenteral use, or their long half life, they are far from being ideal anticoagulants. Ximelagatran, a promising drug, a direct inhibitor of thrombin seemed to be a step forward, but the appearance of undesirable side effects led to its withdrawal. However, this line of investigation has remained open, as such that we now have data from clinical trials that back it up: the direct inhibition of thrombin and activated factor X. These two different mechanisms of action are showing promising results, in that the direct inhibitors of thrombin (dabigatran, hirudins...) are showing not to be inferior in efficacy and safety to enoxaparin in the primary prophylaxis of venous thromboembolism. Similarly, the activated factor X inhibitors (Rivaroxaban, Apixaban ) are also showing the same and in some cases, superior in its prevention. This review looks at the mechanisms of action of both pharmacological groups, their effects on haemostasis, and how they are reflected in coagulation times, their pharmacokinetics and pharmacodynamics. These new anticoagulants are nearer to the ideal anticoagulant and may, in the near future, change the panorama of anticoagulation, not only at health level, but also by achieving improved levels in the quality of life of the patients.