Surveillance of patients at risk of developing hepatocellular carcinoma (HCC) is based on ultrasound (US) examinations performed at either 6 or 12 month intervals. Early detection of HCC in patients with cirrhosis is a challenging issue, since the different entities that are involved in the multi-step process of hepatocarcinogenesis--such as low-grade and high-grade dysplastic nodule--share common US features. Contrast-enhanced US allows reliable detection of arterial neoangiogenesis associated with a malignant transformation. Several reports have shown that the ability of contrast-enhanced US to diagnose HCC currently approaches that of optimized multidetector computed tomography (CT) or dynamic magnetic resonance (MR) imaging protocols. The use of contrast-enhanced US to characterize nodular lesions in cirrhosis has been recently recommended by the clinical practice guidelines issued by the European Federation of Societies for Ultrasound in Medicine and Biology and the American Association for the Study of Liver Diseases. However, contrast-enhanced US has not resulted in any significant improvement in the ability of US to detect small tumor foci, since a comprehensive assessment of the whole liver parenchyma cannot be accomplished during the short duration of the arterial phase. Hence, CT or MR imaging are still mandatory for proper intrahepatic staging of the disease.