The rapid evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome is of great clinical relevance. Biomarkers have become increasingly important in this setting to supplement electrocardiographic findings and patient history because one or both can be misleading. Today, cardiac troponin is still the only marker used routinely in this setting due to its myocardial tissue specificity and sensitivity, as well as its established usefulness for therapeutic decision making. However, even current generation troponin assays have certain limitations such as insufficient sensitivity for diagnosing unstable angina. Novel high-sensitivity assays for cardiac troponin have the potential to overcome these limitations. Further studies are needed to answer some critical questions regarding the best cutoffs for diagnosis and risk assessment and the optimal work-up for rule-out of acute myocardial infarction. Other nonmyocardial tissue-specific markers might help in this setting. Myeloperoxidase, copeptin, and growth differentiation factor 15 reflect different aspects of the development of atherosclerosis or acute ischemia. Each has demonstrated impact in risk stratification of acute coronary syndromes. Limited data also show that copeptin may, when used together with cardiac troponin, improve the sensitivity for diagnosing acute myocardial infarction, and growth differentiation factor 15 may help in selection of patients that benefit from invasive therapy. Further evaluation is needed before these markers can be adopted routinely in clinical practice.