Cell therapy is a promising option for the treatment of ischemic diseases. Infusion or injection of stem or progenitor cells has improved neovascularization and heart function after ischemia in various experimental studies and clinical phase II and III trials. One potential limitation for cell therapy is a low rate of engraftment and persistence of cells in the ischemic tissue. Moreover, impairment of the number and function of patient-derived progenitor cells might limit the efficiency of autologous stem cell therapy. Therefore, strategies to augment cell function, survival, and homing could be crucial to improve success rates for cell therapy. Experimental studies have provided novel options for improving survival and function by transduction of stem or progenitor cells with prosurvival genes (e.g. Akt or telomerase). Pretreatment of cells with small molecules, such as statins, p38 inhibitors, or endothelial nitric oxide synthase enhancers, has been used to augment cell homing, integration, and functional recovery after induction of ischemia. Priming of the tissue by mechanical activation or application of growth factors might further improve recruitment and incorporation of cells. In this article we summarize the experimental studies providing novel concepts for cell-enhancement strategies to aid the treatment of peripheral artery occlusive and ischemic heart disease.