This paper presents the physiology of hemostasis and the coagulation cascade that leads to the formation of a fibrin clot. It highlights the presentation of natural mechanisms against excessive activation of this system and prevention of the consequences of inappropriately activated clot formation in undamaged vessels, as well as the drugs that serve the same function. These drugs include antiplatelet drugs, which reduce the progression of plaques in the arterial system and prevent thrombosis at the site of placement of arterial stents, and anticoagulant drugs that reduce the formation of clots in the venous system and thus prevent venous thromboembolism, such as deep vein thrombosis and pulmonary embolism. Anticoagulant therapy is also used in patients with mechanical heart valves, to prevent systemic embolism in atrial fibrillation, and more recently in the treatment of peripheral vascular disease. The paper presents the most commonly used drugs from each group, with a special emphasis on the direct (new) oral anticoagulant drugs, which are divided into factor Xa inhibitors and thrombin inhibitors. Detailed descriptions are provided of the methods and drugs used to reverse the effects of anticoagulant drugs, their dosages, indications for use, available research results demonstrating the superiority of one agent over another, and the introduction of the first available specific antidotes for the new anticoagulant drugs, which allow the coagulation cascade to proceed normally, thereby preventing bleeding in specific indications and reducing side effects through direct action on the active substance in the drug being reversed.