Heart failure and kidney disease often coexist, and each of the two conditions may lead to progression of the other. Kidney dysfunction is an independent prognostic factor in patients with either acute or chronic heart failure. Worsening renal function may be related with poorer outcomes as well. Multiple mechanisms are involved in the cardio-renal interaction, including hemodynamic abnormalities, neurohormonal and inflammatory activation, oxidative stress, anemia, and abnormalities in mineral and vitamin D metabolism. Serum creatinine has limitations for the assessment of kidney function in patients with heart failure as its short-term changes are dependent on hemodynamic changes and fluid status. New biomarkers of glomerular and tubular function might allow an earlier and more accurate detection of worsening renal function.