Reperfusion therapy has significantly improved survival and prognosis of patients with acute myocardial infarction. However, the development of heart failure, particularly in patients after a large myocardial damage, remains a major challenge. Cell therapy may provide a novel therapeutic option to modify left ventricular remodeling processes and prevent post-infarction heart failure. Experimental studies have suggested that the infusion of different subsets of bone marrow-derived progenitor cells, circulating endothelial progenitor cells, or tissue-residing stem cells improved neovascularization and cardiac function. Clinical studies at present predominantly used bone marrow mononuclear cells (BMNC) isolated from bone marrow aspirates by density gradient centrifugation. Intracoronary infusion of BMNC significantly increased global or regional ejection fraction and/or reduced infarct size and endsystolic volumes in patients with acute myocardial infarction as demonstrated in initial pilot trials and in randomized studies. We aim to review the existing evidence of the beneficial effect of BMNC infusion as well the controversial issues regarding this promising novel therapeutic approach.