Stem cell therapy is regarded as an innovative strategy to intervene in degenerative heart disease. The efficacy of stem cell therapy to regenerate ischemic myocardium has been limited by inadequate numbers of injected cells, unacceptable cell engraftment or long-term survival, and from restrictions associated with the method of delivery. In this review, we provide an overview of the literature emphasizing several strategies which enable improved results after cell therapy for ischemic heart disease. Enhanced cell therapy includes (a) combination of cell grafts either pre-co-cultured or co-injected cells, (b) transplantation of genetically modified cells, or (c) simultaneous administration of control released growth factors, (d) cell preconditioning, (e) use of adjunctive systemic therapy, or (f) repetitive cell therapy. Future studies should focus on the development of strategies for optimization of cell delivery, which will enable easy isolation of adequate cell volume and optimal functional results.