A rise in the intracellular calcium (Ca²⁺) concentration is a major component of the signaling mechanisms regulating platelet function in thrombosis and hemostasis. Previous studies, however, failed to identify many key molecules regulating Ca²⁺ signaling in platelets. Here, we review recent findings, which identified CalDAG‐GEFI as a critical Ca²⁺ sensor that links increases in intracellular Ca²⁺ to integrin activation, TxA₂ formation, and granule release in stimulated platelets. Furthermore, we summarize work that lead to the discovery of STIM1 and Orai1 as key regulators of store‐operated calcium entry (SOCE) in platelets. A short discussion on the usefulness of each molecule as a potential new target for antiplatelet therapy is included.