PURPOSE OF REVIEW: The pathophysiology of heart failure (HF), a complex and heterogenous condition, remains to be fully understood. Troponin and b-type natriuretic peptide are the only biomarkers that are utilized in clinical practice for HF clinical management. Recent advances in proteomics present a powerful tool to identify risk markers and ultimately, potential molecular mechanisms underlying HF pathogenesis. Herein, we explore traditional and novel heart biomarkers, highlighting their potential role in the pathogenesis of HF. RECENT FINDINGS: Recent proteomic analyses have identified numerous proteins including Galectin-3, sST2, GDF-15, FGF21, Endotrophin, THSB-2, ADAMSTL, SVEP1, and anthracycline that are associated with clinical outcomes in HF. These biomarkers are not presently utilized in HF management but may be useful in the future for prediction of death or HF hospitalization. While traditional biomarkers remain essential, proteomic strategies have revealed additional targets that require further mechanistic exploration. Future research should focus on validating these biomarkers and translating proteomic insights into clinical practice to enhance HF management.