Several types of cardiovascular cells use microRNA-21 ( miR-21 ), which has been linked to cardioprotection. In this study, we systematically reviewed the results of published papers on the therapeutic effect of miR-21 for myocardial infarction. Studies described the cardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic, and anti-inflammatory mechanisms. Results suggest that cardioprotective effects of miR-21 may work synergistically to prevent the deterioration of cardiac function during postischemia. However, there are other results that indicate that miR-21 positively regulates tissue fibrosis, potentially worsening a postischemic injury. The dual functionalities of miR-21 occur through the targeting of genes and signaling pathways, such as PTEN , PDCD4 , KBTBD7 , NOS3 , STRN , and Spry-1 . This review provides insights into the future advancement of safe miR-21 -based genetic therapy in the treatment of myocardial infarction.