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In addition to their pivotal role in hemostasis, platelets are an integral part of inflammation. Growing evidence suggests that platelets are a key component of innate and adaptive immune responses. Better understanding of the mechanisms linking platelet function to chronic inflammatory tissue damage may reveal novel targets of therapeutic intervention in immune-mediated and/or inflammatory disorders. The functional interplay between platelets and inflammation is closely implicated in the pathophysiology of a variety of human diseases. This review discusses the relationship between platelets and inflammatory and immune responses across a wide range of conditions in internal medicine.