Cardiac and renal disease frequently coexist but have long been difficult to diagnose in a timely manner and treat effectively. Noninvasive and cost-effective biomarkers are needed to help identify cardiac patients who are at risk of acute kidney injury early in the course of disease. Biomarkers can provide insights into underlying mechanisms and lead to a better understanding of complex disease states such as the cardiorenal syndrome, which can lead to better therapies and, ultimately, to improved patient outcomes. The natriuretic peptides are established biomarkers in heart failure and have set the standard for how a well-validated biomarker can be useful for diagnosis/prognosis, monitoring response to therapy and chronic disease management. For patients with acute kidney injury in the setting of cardiac disease, new biomarkers such as neutrophil gelatinase-associated lipocalin, cystatin C, kidney injury molecule-1 and IL-18 are emerging as early signals of renal dysfunction prior to any elevations in serum creatinine. Other promising candidate biomarkers for the early diagnosis of acute kidney injury include osteopontin, N-acetyl-b-d-glucosaminidase, stromal cell-derived factor-1 and exosomes. More research with all of these novel biomarkers is needed; however, the early results are very promising.