Cardiac troponin is the biomarker of choice for the diagnosis of acute myocardial infarction. Recent consensus recommendations have adopted a concentration of troponin above the 99th percentile of a healthy population to diagnose myocardial infarction. Until recently, there was no assay capable of achieving recommended precision; however, with the development of “highly sensitive” troponin assays, it is now possible to accurately measure troponin concentrations at and below the current 99th percentile of a healthy population. These assays have enormous potential in not only identifying more patients with acute myocardial infarction, and providing superior risk prediction in those so afflicted, in addition highly sensitive troponins assays may be useful for long-term risk assessment of the patient with coronary disease. In this article, we will review the clinical applications, novel concepts, challenges, and limitations of using highly sensitive troponins assays.