Platelets are small, anucleate cell fragments derived from megakaryocytes (MK) in the bone marrow. They are traditionally recognized for their essential role in hemostasis, the process that prevents excessive bleeding following vascular injury. In this capacity, platelets adhere to the site of injury, form aggregates, and facilitate clot formation. Like the immune system, platelets sense danger at the vascular wall. Beyond their hemostatic functions, however, there is now a voluminous body of literature that highlights their critical role in immunity. This chapter aims to explore the intricate relationship between platelets and immune responses, detailing the cellular and molecular mechanisms through which platelets contribute to innate and adaptive immunity, the interaction of platelets with pathogens, and the implications of platelet–immune cell interactions in diseases.