Abstract Behçet's disease (BD) is a widespread occlusive-type vasculitis with life-threatening manifestations. The vasculopathy of BD is unique and any type of vessel can be involved. Moreover, vascular lesions in BD represent an occlusive nature suggesting a hypercoagulable/prothrombotic state. The data concerning the genetic defects of the coagulation cascade are expanding. There is evidence of universal activation of haemostatic system in BD. Procoagulant markers of thrombosis are elevated reflecting intravenous excessive thrombin formation. Defective fibrinolysis with impaired fibrinolytic kinetics may have a role in the hypercoagulable/prothrombotic state of BD. Endothelial cell injury and/or pathological activation is well documented in BD. The aim of this paper is to review current literature knowledge and our experience regarding the unresolved complicated issues of genetic thrombotic defects, in vivo haemostatic markers, coagulation inhibitors, impaired fibrinolysis, and endothelial injury/dysfunction of the hypercoagulable/prothrombotic state of BD. The clinical aspects of vascular thrombosis, the genetic basis of coagulation, coagulation inhibitors, fibrinolysis inhibitors, and endothelial dysfunction are reviewed. Challenges and future prospects regarding the prothrombotic state of BD are discussed together with new promising antithrombotic and antiplatelet treatment strategies. Better understanding of the exact pathogenesis of the hypercoagulable/prothrombotic state of this disease may help to develop novel therapeutic approaches offering a better outcome for Behçet's patients with thrombosis.