Despite state-of-the-art therapy, clinical outcome remains poor in myocardial infarction (MI) patients with reduced left ventricular (LV) function with yearly mortality rates of similar to 15% and rehospitalization rates for heart failure or recurrent infarction within the first year exceeding 20%. Progenitor cell-mediated repair of the damaged heart is a promising new development in cardiovascular medicine. Progenitor cells residing in bone marrow and presumably also in the heart are capable of improving LV function in preclinical MI models but underlying mechanisms remain incompletely understood. Recent placebo-controlled, randomized bone marrow cell transfer trials in MI patients have shown augmented recovery of global LV function of variable magnitude. The observed changes were associated with a favourable effect on myocardial perfusion, with greater infarct size reduction, or with enhanced regional contraction in the infarct border zones. There is now growing consensus that these beneficial effects of bone marrow-derived progenitor cell transfer, as applied in post-MI patients thus far, occur independent of cardiomyocyte formation. At the same time, we have recognized that insufficient homing and survival of transplanted cells into the ischaemic milieu limits the full potential of cell-based cardiac repair. A better understanding of underlying molecular mechanisms of these critical steps in cell-based repair will, however, facilitate the development of improved clinical strategies to enhance functional recovery after myocardial infarction in the years to come.