Due to their tissue specificity and ease of detection, the cardiac troponins (cTn) have emerged as the most important and most utilized biomarkers for the diagnosis of acute myocardial infarction (AMI). The recent achievement of greater sensitivity by cTn assay systems, however, has resulted in the detection of cTn in a wide array of medical conditions, highlighting myocardial cellular necrosis as a feature in several, seemingly unrelated medical conditions, yet complicating the interpretation of a positive test. Since elevated cTn levels are associated with worse clinical outcomes and, thereby, influence medical decisions, careful consideration should be given to the method by which these biomarkers are measured, the patient population on which the test is being applied, and applicable thresholds based on particular clinical conditions. The objective of this review is to trace the clinical evolution of the cTn biomarker from a test for AMI to a general marker of myocardial cellular necrosis with clinically important prognostic information.