Thrombus lysis is the consequence of a restricted number of reactions localised on the surface of fibrin and cell membranes. A functional defect or an insufficient fibrinolytic response may result in thrombosis with severe or fatal clinical consequences. Despite this clinical exigency and a real progress in the knowledge of the different components of this system (plasminogen activators, inhibitors and receptors) including structure-function relationship unveiled by the crystal structure of plasminogen, the functional evaluation of fibrinolysis still remains a challenge in haemostasis. Interestingly, we recently discovered that circulating membrane microvesicles might be indicators of the fibrinolytic response to an inflammatory or prothrombotic process via their participation in a new mechanism of plasmin formation requiring a cross-talk between two different surfaces. We propose that the fibrinolytic activity conveyed by microvesicles could be the real source of fibrinolysis in circulating blood.