Cardiac troponins are the preferred biomarkers for diagnosis of myocardial infarction because of their high sensitivity and specificity for myocardial injury. However, acute and chronic conditions distinct from acute coronary syndromes (ACS) commonly lead to small elevations in troponin levels, with few data available regarding management of care for patients with such conditions. Recently developed highly sensitive troponin assays will likely lead to a substantial increase in the proportion of detectable troponin levels attributable to non-ACS conditions. Novel algorithms with highly sensitive assays, incorporating baseline troponin values and changes in values over 1 to 2 hours, may allow rapid exclusion of myocardial infarction and help to address specificity concerns but must be validated in appropriate target populations. Enhanced detection of very low troponin levels with highly sensitive assays has made feasible several potential new indications for troponin testing, including in the ambulatory setting, where assessment for low-level chronic myocardial injury may enhance risk stratification for heart failure and cardiac death.