Now that we face in the field of Cardiovascular Reparative Medicine a time of reflection and careful thinking and planning of future directions, another work has been published which denies the relevant contribution of exogenous stem cells to increase the pool of functional cardiomyocytes in a rodent model of myocardial ischemia/reperfusion. The authors investigated the mechanism of action of intracardiac injections of fractioned bone marrow mononuclear cells and cardiac progenitor cells by comparing it to the one of a non-cellular activator of the innate immune response (zymosan). All these products improved cardiac function to the same extent, by inducting a CCR2+ and CX3CR1+ macrophage-based response, but not by producing new beating myocardial cells. Benefits of this acute immune response included modifications of the fibroblast activity, a reduction of the extracellular matrix formation and an improvement in the mechanical properties of the scar border zone. This work sheds light on important cellular and immunological pathways to target with future reparative products.