Cardiac biomarkers such as troponins and natriuretic peptides are routinely used in human medicine for the evaluation of myocardial damage and heart failure. Recently, these markers have also been introduced in veterinary medicine. Comparison between human and equine cardiac biomarker studies show important species differences, which can partly be explained by variations in physiology or pathophysiology. Most important are physiological differences in heart rate, cardiovascular response to exercise, food and water intake, and molecular elimination in plasma. Pathological differences are even more prominent. In humans, troponins and natriuretic peptides are mostly used for the diagnosis of acute coronary syndromes and heart failure. These cardiac entities, however, are rare in horses. In this species, cardiac biomarkers are rather proposed for the assessment of valvular or myocardial disease. In conclusion, these species differences corroborate that extrapolation of cardiac biomarker data should always be performed with caution and species-specific data should be applied whenever possible.