Localization of plasminogen and plasminogen activators on cell surfaces promotes plasminogen activation and serves to arm cells with the broad spectrum proteolytic activity of plasmin. Cell surface proteolysis by plasmin is an essential feature of physiological and pathological processes requiring extracellular matrix degradation for cell migration  (1,2)  including macrophage recruitment during the inflammatory response (3), tissue remodeling (4), wound healing  (5,6), tumor cell invasion  (7) and metastasis and skeletal myogenesis (8). Cell associated plasmin on platelets and endothelial cells is optimally localized for promotion of clot lysis. In more recently recognized functions that are likely to be independent of matrix degradation, cell surface-bound plasmin participates in prohormone processing  (9,10) as well as stimulation of intracellular signaling (11-14). This issue of Frontiers in Bioscience on Plasminogen Receptors encompasses chapters focusing on the kinetics of cell surface plasminogen activation (15) and the regulation of plasminogen receptor activity (16)  as well as the contribution of plasminogen receptors to the physiological and pathophysiological processes of myogenesis, muscle regeneration and cancer (17-19). The molecular identity of plasminogen receptors is cell-type specific, with distinct molecular entities providing plasminogen receptor function on different cells. This issue includes chapters on the well studied plasminogen receptor functions of α-enolase, cytokeratin 8, annexin II, S100A10 and annexin A2 heterotetramer (17,19-21). In this introductory chapter, we emphasize challenges and future directions in the field.