Anticoagulant therapy includes unfractionated heparin and vitamin K antagonists' administration. In both of these two types of drugs a treatment failure could occur. Currently available anticoagulants have a numerous disadvantages which could be involved in causes of their malfunctioning. During every new event of the re-thrombosis it is necessary to analyse all circumstances which influence this unfavourable outcome. Firstly, cases during adequate and non-adequate therapy should be distinguished. Secondly, it is important to identify the reasons of the treatment failure. Cancer and/or antiphospholipid antibodies are the main causes of re-thrombosis during adequate therapy. The conditions, which could steer for to non-adequate anticoagulation are various, and their identification could be difficult. The most important thing in this process is the objective documentation of the re-thrombosis. More efficacious, safer, and easier to use anticoagulants are under development. Some of them could bring a problem solution for these patients who underwent anticoagulant treatment failure.