Although drugs exist for the primary and secondary prevention of thrombosis, more potent antiplatelet drugs with sufficiently wide therapeutic windows to avoid bleeding complications are needed. Both academic and pharmaceutical laboratories are working to develop such drugs. This chapter reviews the potential of inhibiting interactions between von Willebrand factor (vWF) and the second most abundant receptor on the platelet, the glycoprotein (GP) Ib/IX/V complex, interactions that are essential for the activation of circulating platelets, contacting a vessel wall injury. Although still at the level of preclinical testing, this area is expected to progress quickly during the next few years, also in view of the three-dimensional structural information that has recently become available and that allows a molecular understanding of vWF binding to the GPIbalpha chain of the GPIb complex.