Platelets play an important role in cardiovascular thrombosis as well as in many other pathological conditions such as inflammation, atherosclerosis and cancer. While multi-target strategies to treat complex diseases are gaining considerable attention, current development of antiplatelet therapies is mostly oriented towards several single targets, arising from our present understanding of the regulation of platelet activation. Limited efforts to develop multi-target agents or multidrug therapies are mostly due to a lack of a systematic basis to define target combinations with synergistic effects. Here we discuss the perspective to use high content phenotypic screening of in vitro models as a potential source for inference of synergetic multi-target strategies to control platelet activation.