The cardiorenal syndrome (CRS) indicates how close the relationship is between heart and kidney during failure of these organs. At present, the classification of the syndrome includes five types of CRS: types I and II which are strictly related to initial heart failure (both acute and chronic), types III and IV which include initial kidney failure, and type V which includes several systemic diseases. Many pathophysiological pathways have been described illustrating how heart and kidney disease are involved in clinical conditions. The diagnosis of CRS is based on both blood tests and ultrasound imaging. Several biomarkers indicating levels of heart and kidney function have emerged over the last few decades which can be used to predict kidney failure in patients with acute or chronic heart disease. Kidney injury biomarkers have also to be tested, especially those indicating glomerular and tubular damage. Renal ultrasound and trans-thoracic echocardiography can provide further information on heart and kidney failure in patients with cardio-renal syndrome at any stage.