Clinicians must be aware that all troponin assays are not created equal, and they must understand the characteristics and potential limitations of the specific assay used in their practice. This is because the susceptibility of troponin assays to potential interfering substances, such as heterophile antibodies and rheumatoid factor, can vary widely. Cardiac troponin is a complex analyte, and the regions of the troponin molecule targeted by the antibodies comprising these immunoassays are an important consideration for assay performance. Furthermore, assays have become, over time, increasingly sensitive, with improved analytical precision. This has resulted in a wide spectrum of assay quality in practice. Ultimately, this variability in quality has led to confusion in clinical practice and in the literature because varying cutoffs and decisions limits have been used. These decision limits have not always been the same for a given assay or between users of the same assay, and some have changed between earlier and later generations of the same assay. Thus, one study may not be comparable to the next in a similar population, and a test in one hospital may not have the same meaning in another. Assays are heterogeneous in their ability to accurately and reliably measure in the range of the 99th percentile of troponin values (i.e., the 95% confidence interval [CI] can be rather narrow for some assays but much wider for others) (14). Different interpretations of a “reference control population” upon which the 99th percentile of cardiac troponin values is based further complicates interpretation. Finally, measurement of cardiac troponin is not currently standardized. Therefore, unlike glucose, total cholesterol, and many other common measurements, troponin values vary from assay to assay, and assays have very different values for 99th percentile of normal. The NACB has developed analytical recommendations for troponin assays (15), and 1 publication has proposed a system of “grading” assays (16). With a centrally maintained, continuously updated database of assays, their functional characteristics and overall “grade” on these parameters would facilitate assay selection through competitive pressure to promote assay quality. Importantly, for the multiple troponin I assays in existence, regulations to ensure standardization of assays to the National Institute of Standards and Technology reference material (NIST #2921) would make it more feasible for clinicians to readily compare troponin levels measured in different laboratories or hospitals with different assays or generations of assays. This may be particularly important as patients are transferred from one facility to another. It is recommended that reference interpretive thresholds should be established for each cardiac biomarker, based on a population of normal, healthy individuals without a known history of heart disease. Creation of a healthy subject sample bank—such that all assay manufacturers could establish the 99th percentile of their assay against a common standard population of uniform size and clinical characteristics—would eliminate variability related to the population selected and obviate the need for each hospital or clinic to independently carry out this task. The NACB analytical document also recommends 1 threshold for optimal use of the cardiac biomarkers, troponin I and troponin T. Importantly, assays for cardiac biomarkers should improve towards a total imprecision (% coefficient of variation) of <10% at the 99th percentile reference limit. Even now, “high-sensitivity” troponin assays are being developed and are in use in some areas of the world. These assays have substantially lower limits of detection (in the picogram per milliliter range versus the current fourth-generation assays in the nanogram per milliliter range) as well as improved assay precision. Clinicians, laboratorians, clinical pathologists, and other users must communicate to assure that their troponin assays are in sufficient compliance with these recommendations and that all groups understand the characteristics of the assay in clinical use at a given facility.