Cardiorenal syndrome (CRS) refers to pathophysiologic interaction of the heart and kidney and is associated with acute kidney injury (AKI) and high mortality. Cardiac surgery or acute decompensated heart failure and radiocontrast-induced nephropathy are common clinical scenarios of CRS. Unfortunately, established functional biomarkers of glomerular filtration rate such as serum creatinine, urea, and diuresis delay AKI diagnosis by 24 to 48 hours. Novel renal biomarkers indicating tubular injury are emerging and may have wide implications. This review focuses on several novel renal biomarkers with the most promising biologic characteristics and clinical evidence for their AKI predictive ability: neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin 18, and fatty acid-binding proteins. The value of each biomarker is reviewed on currently available clinical data in typical settings of CRS. These markers might extend the therapeutic window during which timely and individualized patient management might be possible.