Chemokines are a family of small proteins that have significant roles in inflammation, angiogenesis and cellular homing. Since inflammation and hemostasis/thrombosis have multiple overlapping roles and pathways, one could expect that some chemokines would also have biologically significant roles in hemostasis/thrombosis as well. This would especially be true for chemokines that are localized solely or predominantly within platelets and released in large amounts at sites of platelet activation such as platelet factor 4 (PF4, CXCL4) and its closely related chemokine, platelet basic protein (PBP, CXCL7). Our group and others have clearly demonstrated an in vivo role for PF4 in hemostasis/thrombosis, but not for PBP, which in contrast has clear proinflammatory properties. This review will focus on PF4 and its potential roles in hemostasis/thrombosis and the underlying pathways by which PF4 may be especially important in such pathologic thrombotic states as heparin-induced thrombocytopenia (HIT) and septic shock.