Evidence suggesting that bone marrow and circulating blood may harbor myocardial and vascular progenitor cells was the basis for pre-clinical studies of cell therapy for acute myocardial infarction (MI). Rapid initiation of clinical trials has since followed, with regional myocardial delivery of autologous cells being tested as adjunctive therapies for both acute and chronic left ventricular dysfunction. While clinical cell transplantation trials originally began with the explicit goal of myocardial regeneration, more recently the emphasis has shifted to attempted modulation of myocardial remodeling through other processes, such as mechanical strengthening of scar tissue and promotion of myocardial tissue survival through cellular paracrine effects. This article discusses the scientific rationale for cell therapy strategies in acute MI and provides an overview of the clinical studies that have been undertaken to date.