In the case of suspected acute coronary syndrome and myocardial infarction positive diagnosis or exclusion strongly depend on the use of biomarkers and in particular cardiac troponins (cTn). Especially in the early phase of myocardial infarction the sensitivity of cTn assays has been unsatisfactory. This has led to the investigation of many other potential markers for the early diagnosis of myocardial infarction. In addition, several traditional markers have been advocated, e.g., myoglobin, as these were considered to be more sensitive than cTn. With the advent of high-sensitive (hs) cTn assays the value and practical use of the alternative or additional markers has to be reassessed. According to the currently available data, no single marker is superior to hs-cTn for the diagnosis of acute myocardial infarction. In particular, the notion of superior sensitivity of myoglobin compared to cTn no longer holds true. There are two protein markers, hearttype fatty acid binding protein and copeptin, and plasma free fatty acids that may increase the diagnostic value and specifically the negative predictive value when determined on admission in combination with hs-cTn. However, the incremental gain, if any, is small. Further data are needed to determine, whether these markers can in fact improve diagnosis and if they are superior to the recommended use of the relative or absolute change of hs-cTn after 3 h.