Recent experimental data suggest a role for blood-borne mononuclear cells, including bone marrow-derived endothelial progenitor cells (EPCs) in organization, vascularization, and recanalization of thrombi. Older studies have described in detail the in situ structural modifications accompanying these processes. The common themes are (a) involvement of pluripotent mononuclear cells, and (b) proteolytic and/or phagocytic activity of monocytes/macrophages (MCs/Mphs) in modifying the thrombus to a proangiogenic state. In addition to a nurturing function, MCs/Mphs may assist the engraftment of thrombus-trapped or incoming EPCs. The differences between the recanalization potency of venous and arterial thrombi suggest that in addition to the organization of the fibrin meshwork, the cellular composition of the venous thrombi may be responsible for the better recanalization seen in venous clots. These observations set the stage for therapeutic manipulation of organization and recanalization of thrombi, by increasing the MC/Mph and/or EPC content.