Cardio-renal syndrome (CRS) is a frequent and life-threatening syndrome. It is a disorder of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Acute kidney injury (AKI) is strongly associated with increased morbidity and mortality in patients with CRS. Early detection of renal dysfunction is not possible using the traditional marker, serum creatinine, and therefore efforts to explore possible biomarkers for early detection of AKI are being made. Apart from predicting AKI, several biomarker studies also identified predictors for poor prognosis such as the need for renal replacement therapy (RRT) or death. It is possible that biomarkers can become risk factors in an improvement of clinical outcomes of CRS. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with renal dysfunction and the treatment for this disease can be modified based on cardiac biomarkers. In addition to natriuretic peptides, which are established cardiac markers, several new biomarkers have been identified and may play important roles in CRS. In this review, we will briefly summarize the literature on novel renal and cardiac biomarkers and discuss their potential roles in the clinical outcome of CRS.