At the dawn of the new century, the advent of more specific myocardial tissue markers, such as cardiac troponin I (cTnI) and T (cTnT), has led to a new definition of acute myocardial infarction (AMI) by international guidelines. If we accept the concept that AMI is the portion of acutely necrotic myocardial tissue (irrespective of size), some patients previously diagnosed with severe angina may be currently considered to present minimal (even microscopic) quantities of myocardial necrosis. Although increased cTnI or cTnT values always indicate myocardial tissue damage, a positive test is not able to identify the mechanism responsible for that cardiac damage (which could be not due to ischemia). New cTnI and cTnT immunoassays with increased analytical sensitivity may increase "false positive" results in patients with cardiovascular disease, especially those with advanced age, heart failure (HF), severe comorbidities (such as chronic renal insufficiency), or assuming potential cardiotoxic drugs. Hence, it may be not clear for most patients and physicians whether high-sensitivity cTnI and cTnT methods will lead to more clarity or confusion. The aim of this review is to update the present knowledge in the field of cTnI and cTnT with particular attention on the impact of immunoassays with increased analytical sensitivity on both laboratory and clinical practice.