In the last decade, new imaging techniques have become available, offering the possibility of investigating contrast perfusion of liver nodules in cirrhosis. It is now accepted that a non-invasive diagnosis of hepatocellular carcinoma (HCC) can be established based on the vascular pattern, obtained with pure blood pool contrast agents. The diagnostic pattern includes: hypervascularity in the arterial phase (15–35 s after contrast injection), consisting in a contrast signal in the nodule greater than in the surrounding parenchyma, followed by contrast wash out, which leads the nodule to show the same, or, more specifically, a lower contrast signal, than the surrounding parenchyma in the portal and late phases (>40 s after injection). Such a pattern can be obtained not only by computed tomography or magnetic resonance imaging, but also by contrast-enhanced ultrasonography, most simply with real-time low mechanical index harmonic imaging ultrasound equipment with second-generation ultrasound contrast agents. The risk of false-positive diagnosis of malignancy isnearly abolished when the functional vascular pattern is not the only feature, but is superimposed on a nodule visible also without contrast. One single contrast imaging technique may suffice to make a diagnosis of HCC if the nodule is >1 cm in diameter and has developed during a surveillance program. Other types of contrast agents, such as those taken up by the reticular-endothelial system cells, may offer additional diagnostic clues, but definitive evidence of their efficacy is still to be produced. In conclusion, contrast-enhanced imaging techniques now offer the possibility of a non-invasive diagnosis of HCC in a large number of cases, reducing the need of invasive investigations, such as ultrasound-guided biopsy or angiography.