Collagen is a unique agonist of platelets, because it acts as an immobilized ligand that only causes platelet activation after stable adhesion. This review addresses the present understanding of how platelet interaction with collagen supports the process of thrombin generation and coagulation. Only some of the collagen-adhered platelets, that is, those showing profound changes in shape and shedding microparticles (resembling apoptotic cells), appear to contribute to the procoagulant activity of platelets. The main signaling receptor for collagen, glycoprotein VI, plays a key role in the platelet procoagulant response during thrombus formation; this is a reason why new anti-glycoprotein-VI antibodies are promising antithrombotic tools.