Ultrasound is the most commonly used liver imaging modality worldwide. Unfortunately, ultrasound has limited sensitivity in the detection of small tumour nodules. Moreover, ultrasound findings are often non-specific, as there is enough variability and overlap in the appearance of benign and malignant liver lesions to make a definite distinction problematic. Recently, the introduction of microbubble contrast agents and the development of contrast-specific techniques have opened new prospects in liver ultrasound. The advent of second-generation agents that have higher harmonic emission capabilities has been instrumental in improving the easiness and the reproducibility of the examination. Over the past few years, several reports have shown that real-time contrast-enhanced ultrasound can substantially improve detection and characterization of focal liver lesions with respect to baseline studies. With the publication of the guidelines for the use of contrast agents in liver ultrasound by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), contrast-enhanced ultrasound 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. In this paper, we discuss the impact of EFSUMB guidelines on diagnostic protocols currently adopted in liver imaging with regard to four clinical scenarios: (1) characterization of focal liver lesions of incidental detection; (2) diagnosis of HCC in patients with cirrhosis; (3) detection of hepatic metastases in oncology patients; (4) guidance and assessment of the outcome of percutaneous tumour ablation procedures.