Malignancy is an acquired thrombophilic condition associated with a significant risk of thrombosis. Venous and arterial thromboembolism is a common complication for patients with cancer, who also present with a hypercoagulable state, even in the absence of manifest thrombosis. Furthermore, clotting activation may play a role in tumor progression. The pathogenesis of thrombosis in cancer is multifactorial; however, a relevant role is attributed to the tumor cell capacity to interact with and activate the host hemostatic system. Among other factors, the prothrombotic action of antitumor therapies is also important. Thrombotic events can influence the morbidity and mortality of the underlying disease. Therefore, preventing these complications in cancer patients is a clinically relevant issue. Recently, new approaches to the prevention and cure of thrombosis in cancer have been investigated, and the hypothesis that strategies to inhibit clotting mechanism may favorably affect malignant disease is gaining increasing interest. In this article, the various aspects of the complex relationship between thrombosis and cancer, from pathophysiology to therapy, are reviewed.