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Since their discovery, chemotactic cytokines or chemokines have been intensively studied for about half a century. Chemokines originate from tissue cells, leukocytes, blood platelets and plasma. Here, we review a number of seminal findings on plasma chemokines within an historical and international context. These aspects include how induction and purification protocols led to the discovery of a new family of mediators, named chemokines, on the basis of protein sequencing; how molecular cloning techniques facilitated discoveries of additional family members on the basis of conserved protein structures; how blood plasma and platelets were used as a source of inducible and constitutively expressed chemokines; how various forms of proteolytic reactions may convert precursor proteins into chemokines and either potentiate or inactivate their activity; how abundancy classes and synergism should be interpreted through critically considering plasma chemokine biology; and how other blood proteins, such as serum amyloid A, interact in functional terms with CXC and CC chemokines. The gradual dissection of all these elements not only reveals the complexity of chemokine actions, but also stimulates a more comprehensive interpretation of chemokine levels in plasma and serum, with future chemokinome analyses in mind.