Cancer patients develop a hypercoagulable state with a four- to seven-fold higher thromboembolic risk compared to non-cancer patients. Thromboembolic events can precede the diagnosis of cancer, but they more often occur at diagnosis or during treatment. After malignancy itself, they represent the second cause of death. Low molecular weight heparins are the backbone of the treatment of cancer-associated thromboembolism. This treatment paradigm is possibly changing, as direct oral anticoagulants (DOACs) may prove to be an alternative therapeutic option. The currently available DOACs were approved during the first and second decades of the 21st century for various clinical indications. Three molecules (apixaban, edoxaban and rivaroxaban) are targeting the activated factor X and one (dabigatran) is directed against the activated factor II, thrombin. The major trials analyzed the effect of these agents in the general population, with only a small proportion of cancer patients. Two published and several ongoing studies are specifically investigating the use of DOACs in cancer-associated thromboembolism. This article will review the current available literature on the use of DOACs in cancer patients. Furthermore, we will discuss published data suggesting potential anti-cancer actions exerted by non-anticoagulant effects of DOACs. As soon as more prospective data becomes available, DOACs are likely to be considered as a potential new therapeutic option in the armamentarium for patients suffering of cancer-associated thromboembolism.