Early detection and risk stratification of patients with heart failure (HF) are crucial to improve outcomes. Given the complexity of the pathophysiological processes of HF and the involvement of multi-organ systems in different stages of HF, clinical prognostication of HF can be challenging. In this regard, several biomarkers have been investigated for diagnosis, screening, and risk stratification of HF patients. These biomarkers can be classified as biomarkers of myocardial stretch such as B-type natriuretic peptide, biomarkers of neurohormonal activation, biomarkers of inflammation and oxidative stress and biomarkers of cardiac hypertrophy, fibrosis and remodel-ing. In this paper, we summarize current evidence supporting the use of selected biomarkers in HF. We review their diagnostic, prognostic and therapeutic role in the management of HF. We also discuss potential factors limiting the use of these novel biomarkers in the clinical practice and highlight the challenges of adopting a multi-biomarker strategy.