The development and clinical introduction of microbubble contrast agents has had a particular impact on the detection and differential diagnosis of liver tumors. The first approach widely employed made use of high-transmission power ultrasound, which destroyed the microbubbles in the process of imaging them. It is particularly successful for those agents that have a liver-specific post-vascular phase because, like liver-specific agents used in other imaging modalities such as magnetic resonance imaging and nuclear medicine, malignancies do not retain the contrast, so they stand out with very high conspicuity. Used this way with color Doppler or variants of it, more subcentimeter lesions can be demonstrated with ultrasound than with computed tomography. However, the destructive nature of this approach meant that continuous real-time scanning was impossible. Two developments allowed this to be redressed: new classes of microbubbles with perfluoro gasses instead of air and the invention of multipulse scanning modes that are sensitive to the nonlinear (harmonic) responses of the microbubbles and suppresses tissue signals. This low-power approach is now used almost exclusively, and it has the advantage of displaying the arterial phase of blood supply to a mass and a later phase when the bubbles are trapped in the sinusoids so that the vascular volume of the tissue is depicted. Malignancies typically show a low signal intensity in this phase, regardless of whether they are hyper- or hypovascular in terms of their arterial supply. This allows them to be detected with high sensitivity and much more easily than the destructive modes allowed. In addition, the arterial supply that can be now depicted in real time has characteristics that allow most benign masses to be distinguished from each other and from malignancies, thus improving specificity. Microbubbles also can be used as tracers to provide functional information that can detect occult metastases and cirrhosis noninvasively.