Stromal and immune cells and their interactions have gained the attention of cardiology researchers and clinicians in recent years as their contribution in cardiac repair is increasingly recognized. The repair process in the heart is a particularly critical constellation of complex molecular and cellular events and interactions that characteristically fail to ensure adequate recovery following injury, insult, or exposure to stress conditions in this regeneration-hostile organ. The tremendous consequence of this pronounced inability to maintain homeostatic states is being translated in numerous ways promoting progress into heart failure, a deadly, irreversible condition requiring organ transplantation. Fibrosis is in fact a repair response eventually promoting cardiac dysfunction and cardiac fibroblasts are the major cellular players in this process, overproducing collagens and other extracellular matrix components when activated. On the other hand, macrophages may differentially affect fibroblasts and cardiac repair depending on their status and subsets. The opposite interaction is also probable. We discuss here the multifaceted aspects and crosstalk of this cell dipole and the opportunities it may offer for beneficial manipulation approaches that will hopefully lead to progress in heart disease interventions.