Ultrasonography (US) is the most commonly used liver imaging modality worldwide. Unfortunately, it has limited sensitivity in the detection of small tumor nodules. Moreover, US findings are often nonspecific, as appearances of benign and malignant liver lesions overlap. The introduction of microbubble contrast agents and the development of contrast-specific techniques have opened new prospects in liver US. The advent of second-generation agents that enable continuous real-time contrast-enhanced imaging has been instrumental in improving the acceptance and reproducibility of the examination. With the publication of guidelines for the use of contrast agents in liver US by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), contrast-enhanced US has entered clinical practice. The guidelines define the indications and recommendations for the use of contrast agents in focal liver lesion detection, characterization, and posttreatment follow-up. Recently, the clinical value of contrast US as a reliable alternative to CT or MR imaging in characterizing hepatocellular carcinoma in cirrhosis has been endorsed by the practice guideline document issued by the American Association for the Study of Liver Diseases and the 2005 Monothematic Conference on Hepatocellular Carcinoma of the European Association for the Study of the Liver. In this article, the current role of contrast US in the diagnostic management of focal liver lesions is discussed with regard to the following clinical scenarios: (1) characterization of incidental findings; (2) diagnosis of hepatocellular carcinoma in patients with cirrhosis; and (3) identification of hepatic metastases in oncology patients; (4) guidance and monitoring of tumor ablation procedures.