Hepatocellular carcinoma is a common and lethal cancer occurring almost exclusively in those with chronic liver disease including cirrhosis of any cause and postviral status with hepatitis B virus. Its geographic distribution is related to those geographic regions where viral hepatitis is endemic. However, today, nonalcoholic fatty liver is of increasing importance as an underlying cause and overall, the incidence of HCC is increasing worldwide. Screening with US every six months is an established method for the discovery of tumors while they are still small and treatable, reducing tumor related mortality and downstaging disease at the time of diagnosis. CEUS of HCC is focused on showing the classic enhancement pattern including arterial phase hypervascularity and washout in the portal venous phase. However, HCC develops by a process of stepwise progression of hepatocarcinogenesis whereby regenerative nodules grow with conversion to a dysplastic nodule and eventually a small hepatocellular carcinoma and ultimately a large dysplastic carcinoma. This process is accompanied by a progressive reduction of the normal portal venous and hepatic arterial blood flow while all the while, there is a process of neoascularity in the nodules. These changes are not uniform in all nodules leading to a very varied enhancement, which has association with the degree of differentiation of the tumors. Key aspects include slow and weak washout in the portal venous phase, possibly no washout regardless of the length of the observation and iso and even hypovascularity in the arterial phase. In the final analysis, HCC may have very varied enhancement patterns although the identification of a hypervascular nodule in the arterial phase of enhancement is key. A multimodality approach to the diagnosis of HCC is practiced with current heavy reliance on MRI. However, CEUS has many advantages for diagnosis including superior sensitivity to subtle arterial phase enhancement, real time imaging allowing for appreciation of enhancement regardless of the time of onset, or the duration of the enhancement. As well US with CEUS precludes the problem of arterioportal shunts showing nonspecific arterial phase hyperenhancement on CT and MR scan. These advantages make CEUS an essential component of any program for diagnosis of liver nodules in a cirrhotic liver. CEUS is also invaluable for the guidance of radiofrequency ablation and for surveillance of patients post treatment.