Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.