The diagnosis of acute myocardial infarction currently rests on the measurement of troponin, a biomarker of myocardial necrosis. Unfortunately, the current generation troponin assays detect troponin only 6-9 h after symptom onset. This can lead to a delay in diagnosis and also excessive resource utilization when triaging patients who, ultimately, have noncardiac causes of acute chest pain. For these reasons, there has been extensive research interest in biomarkers that can detect and rule out myocardial infarction early after symptom onset. These include markers of myocardial injury, such as myoglobin, heart-type fatty acid binding protein, glycogen phosphorylase BB; hemostatic markers, such as D-dimer; and finally, inflammatory markers, such as matrix metalloproteinase 9. Recently, highly sensitive troponin assays have reported an early sensitivity for myocardial infarction of greater than 95%, although at a cost of reduced specificity. The optimal strategy with which to use these novel biomarkers and highly sensitive troponins has yet to be determined, and interpretation of their results in light of thorough clinical assessment remains essential.