Acute myocardial infarction (AMI), a common heart disease that may lead to chronic heart failure, is the leading cause of morbidity and mortality worldwide. MicroRNAs (miRNAs) are small non-coding RNAs that mediate the expression of target genes. Recently, a number of miRNAs are emerging as potential biomarkers of AMI. MiRNA-499 is a newly discovered member of miRNAs, and is mainly expressed in myocardium, the circulating levels of miRNA-499 was increased in AMI patients. This review summarizes the latest advances in the miRNA-499 study and discusses the potential of miRNA-499 to be a biomarker of AMI. Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide, thus an effective and accurate diagnostic biomarker would be needed to help decrease the mortality of AMI patients. One of the traditional biomarkers for AMI is troponin. Circulating troponin levels rise around 3 hours after the onset of chest pain, due to the relative delayed release time of troponin. It is widely believed that a rapid and correct diagnosis of AMI has an important impact on patients' treatment and prognosis. Therefore, earlier biomarkers than troponin with both high sensitivity and specificity remain to be needed. MicroRNAs (miRNAs) are endogenous small non-coding RNAs of less than 22 nucleotides that are implicated in nearly all cellular events including cell differentiation and proliferation as well as the pathogenesis of certain human diseases (1,2). Recently, a number of findings support the notion of the implication of miRNAs in the development and progression of cardiovascular diseases (3). The plasma levels of miRNA-1, -133a, -133b, and -499-5p are upregulated in AMI patient, and represent novel biomarkers of cardiac damage. Several reviews have provided an over-view of biology of miRNA-1, miRNA-133b, -499-5p and their involvement in cardiovascular physiology and pathology, and discussed the potential of these miRNAs to become a novel biomarker of AMI and even an effective therapeutics agent (4-8). miRNA-499 is a newly discovered member of miRNAs encoded by myosin gene family, and its expression level in plasma was elevated in the patients with AMI, a common heart disease that is the leading cause of morbidity and mortality worldwide (9). A previous study compared the diagnostic performance of miRNA-499 and some traditional biomarkers like SMB, cTnI, cTnT, CK-MB, CK, LDH, and concluded that miRNA-499 was present in plasma earlier than other conventional biomarkers of AMI, pointing to the likelihood that miR-499 can be a vital molecule in the early diagnosis of AMI. This study also found that the circulating level of miR-499 correlated well with circulating troponin I