The well-known platelet shape change is the universal hallmark of activation. This review uncovers the biophysics underlying this rapid and dramatic transformation. We aim to give a broad vision of the interplay between different cytoskeletal subsystems, which is based on physical considerations and recent advances in mathematics and computational biology. These novel findings lead to the understanding that the ring of microtubules counterbalances cortical tension in the resting platelet, making it a “mechanically charged” system. Platelet activation breaks the balance via several mechanisms, triggering rapid ring buckling and cell rounding. Based on the review of known data concerning the relations between platelet shape and function, we hypothesize that disk-to-sphere transformation facilitates platelet adhesion under flow. Conclusions of the paper may be useful for the development of novel, cytoskeletal-based strategies of antiplatelet therapy.