Heart failure remains a major cause of death and disability, requiring rapid development of new therapies. Bone marrow-derived mesenchymal stem cell (MSC)-based therapy is an emerging approach for the treatment of both acute and chronic heart failure. Following successful experimental studies in a range of models, more than 40 clinical trials of MSC-based therapy for heart failure have now been registered, and the results of completed clinical trials so far have shown feasibility and safety of this approach with therapeutic potential suggested (though preliminarily). However, there appear to be several critical issues to be solved before this treatment could become a widespread standard therapy for heart failure. In this review, we comprehensively and systemically summarize a total of 73 preclinical studies and 11 clinical trial reports published to date. By analyzing the data in these reports, (1) improvement in the cell delivery method to the heart in order to enhance donor cell engraftment, (2) elucidation of mechanisms underpinning the therapeutic effects of the treatment differentiation and/or treatment secretion, and (3) validation of the utility of allogeneic MSCs which could enhance the efficacy and expand the application/indication of this therapeutic approach are highlighted as future perspectives. These important respects are further discussed in this review article with referencing latest scientific and clinical information.