In recent years, numerous biomarkers have been studied in heart failure to improve diagnostic accuracy and identify patients at higher risk. The overall outcome remains fairish despite improvements in therapy, with mean survival after first hospitalization, around 5 years. We therefore need surrogate end points to better understand the pathogenetic mechanisms of the disease, including interplays with other organs. The kidney plays an important role in the initiation and progression of HF, and around one-third of patients with HF show some degree of renal dysfunction. In addition, treatment for HF often worsens renal function, consequently to hemodynamic and clinical improvement do not correspond an effective improvement in HF prognosis. Association between HF and renal impairment (RI) is now classified as cardiorenal syndrome (CRS) pointing out the bidirectional nature of this vicious circle leading to a mutual and progressive damage of both organs. The clinicians can rely on circulating biomarkers that give insights into the underlying pathogenetic mechanisms and help in risk stratification. Recently, a multimarker strategy including biomarker tool to traditional risk scores has been purposed and applied: Although each biomarker provided incremental outcome benefit, the combination of multiple biomarkers should offer the greatest improvement in risk prediction. Natriuretic peptides (NP) and cardiac troponins (TN) are the two biomarkers most studied in this setting, probably because of their organ-specific nature. However, both NP and TN cutoffs in presence of renal dysfunction need to be revised and discussed in relation to age, gender and stage of RI. In this context, the biomarkers are a unique opportunity to elucidate pathophysiological mechanisms, tailor clinical management to the single patient and improve outcomes. Specific studies about the exact role of biomarkers as in HF as in CRS should be planned and considered for future trials.