Hepatocellular carcinoma (HCC) is the leading cause of death in liver cirrhosis. Ultrasound (US) is widely accepted as the screening imaging modality of choice for HCC in patients with a history of chronic liver disease. However, the US characteristics of HCCs are non-specific and thus, other imaging techniques or biopsy are usually necessary to characterize focal liver lesions (FLL) and confirm malignancy. Blood flow to HCC is mainly arterial, making dynamic CT and MRI the most commonly used techniques to detect the characteristic arterial hypervascularization. Recently, the development of second-generation US contrast agents and microbubble-specific software has changed the role of US in real-time evaluation of the macro and microvascularization of FLLs. With this technology, the accuracy of US in the diagnosis of HCC and its differentiation from other FLLs such as regenerating nodules has improved dramatically. In addition, contrast-enhanced ultrasound may also be a useful tool in the staging of HCC and in the evaluation of percutaneous treatment.