Liver metastases and hepatocellular carcinomas are two of the most common causes of cancer deaths in the world. Radiofrequency ablation (RFA) is a well recognized, effective and minimally invasive means of treating malignant hepatic tumors. This article describes the use of contrast-enhanced 3D ultrasound (CE-3DUS) in the staging, targeting and follow-up of patients with liver tumors undergoing RFA. In particular, its value in the management of large hepatic lesions will be illustrated. Current limitations of CE-3DUS and future developments in the technique will also be discussed. In summary, CE-3DUS is useful in the RFA of liver tumors with improved detection and display of occult lesions and recurrence, in the assessment of lesional geometry and orientation for a more accurate planning and guidance of multiple RFA needle electrodes in large tumors and in the evaluation of residual or recurrent disease within the immediate and/or subsequent follow-up periods.