Post-infarction heart failure is closely associated with a major loss of differentiated cardiomyocytes consecutive to ischemia, which cannot be overcome by the poor renewal of cardiac cells in the heart. This has led many investigators to develop various strategies for cell-based therapy to improve defective contractile performance and heart function. Although indirect beneficial effects can be expected from various mechanisms, such as improvement of tissue perfusion, tissue contractility recovery or paracrine secretions, a definitive treatment requires neocardiogenesis in order to repopulate the ischemic area. The concept of cell plasticity opened new perspectives in this field, suggesting a possible use of different adult cells with the aim to achieving cell transdifferentiation towards cardiomyocytes when placed in an appropriate in vivo context. Among the sources of adult stem or progenitor cells for cardiomyocyte regeneration, cells derived from adipose tissue are now being investigated, including at the clinical level. According to several reports, the transplantation of these cells is associated with a functional benefit, which however cannot only be explained by transdifferentiation regardless of the underlined mechanisms. The purpose of this chapter is to discuss, in a critical view, the direct and indirect effects of stromal cells derived from adipose tissue on heart regeneration.