Cell-gene therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. We want to discuss several aspects under intense focus of research required to eventually bring this approach to the clinical setting: 1. the effects of timing and routes of administration of cells post-myocardial infarction (MI) and the efficacy of injectable biopolymer scaffolds to improve cardiac cell retention and function using the rat model; 2. The use of autologous cells as a “vector” to deliver biological therapeutic agents to influence neo-angiogenesis or myogenesis; 3 Strategies attempting to modify the phenotype of pluripotent cells ex-vivo using physical factors prior to cell tansplantation; and finally, early results from the combination of cell therapy associated with incomplete coronary-artery bypass grafting (CABG) or transmyocardial laser revascularization (TMLR) in patients with chronic cardiac ischemic disease.