Targeted therapy is certainly considered the future of cancer treatment. Several new molecules targeting critical intracellular signaling actors, particularly kinases, are arriving in clinics and many other are under development. However, proteins targeted by these drugs are common to many cell types and are particularly implicated in the highly dynamic processes of platelet activation. Therefore, the effects of targeted drugs, including kinase inhibitors, on platelet activation have to be considered in clinical practice. Moreover, their analysis also represents an opportunity to increase our knowledge in platelet biology and physiology and to develop novel antiplatelet strategies. In this review we briefly describe the major platelet signaling pathways that may be affected by these new drugs and discuss some clinical implications of their use.