Understanding of chronic heart failure (HF) has progressed from a syndrome of disordered hemodynamics caused by alterations in the structure of the heart to one that involves intertwined molecular pathways in disarray. Accordingly, the assessment and treatment of patients with chronic HF has shifted from a focus on hemodynamics to modification of maladaptive molecular processes. Accumulating evidence shows that molecular biomarkers of disease could provide a unique window into the pathophysiology of chronic HF, potentially improving our ability to predict adverse outcomes, provide novel drug targets, and even help gauge therapeutic efficacy. The more 'traditional' biomarkers such as cardiac troponin, natriuretic peptides, and C-reactive protein have been studied in large cohorts of patients with chronic HF and have relatively established clinical applications. In this Review, we summarize the properties, clinical data, and potential applications of some emerging biomarkers that could uniquely indicate the level of biomechanical stretch, inflammation, ventricular remodeling, myocardial injury, and renal dysfunction that occurs in chronic HF. We will also discuss the potential role for these biomarkers within a multimarker-based strategy that could, in the future, lead to better care for these patients.