Noninvasive characterization of focal liver lesions is largely based on their enhancement patterns on contrast-enhanced imaging. The use of microbubble contrast agents combined with specialized ultrasound (US) techniques has significantly expanded the role of US in the diagnosis of focal liver lesions based on their vascularity and specific enhancement features. With the advantage of real-time scanning, contrast-enhanced ultrasound (CEUS) can evaluate small lesions that are indeterminate on computed tomography (CT) or magnetic resonance imaging (MR), because CEUS is far less affected by timing issues. Hepatocellular carcinoma is typically characterized by increased arterial flow with frequent dysmorphic tumor vessels and decreased portal venous flow. However, negative enhancement in the portal phase is often not obvious until late (>2 minutes). On the other hand, metastasis shows prompt brief arterial hypervascularity, with either a rim or diffuse pattern and rapid washout, seen as perfusion defects during the portal venous phase. This pattern of complete rapid washout of metastases within the homogeneously enhanced background liver parenchyma can improve their detection and also improve differentiation from hepatocellular carcinoma or benign focal lesions. All malignant lesions generally show negative enhancement or washout during the extended portal venous phase, and this pattern is useful to differentiate them from benign lesions. Microbubble agents, confined to the intravascular space, may infrequently characterize malignancy by showing washout whereas CT or MR shows persistent enhancement due to interstitial distribution.