Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver, usually developing in individuals with chronic liver disease or cirrhosis. Worldwide, it is the fifth most common cancer and the third most common cause of cancer death. There were 156,940 deaths attributed to liver and intrahepatic bile duct cancer in the United States in 2011, with 221,130 new cases diagnosed. The lifetime risk of developing liver and intrahepatic bile duct cancer in the United States is about 1 in 132, with an age-adjusted incidence rate of 7.3 per 100,000 people per year. The American Association for the Study of Liver Diseases (AASLD) recommends surveillance for the following groups at high risk for developing HCC: Asian male hepatitis B virus (HBV) carriers age 40 and older, Asian female HBV carriers age 50 and older, HBV carriers with a family history of HCC, African/North American Black HBV carriers, HBV or hepatitis C virus carriers with cirrhosis, all individuals with other causes for cirrhosis (including alcoholic cirrhosis), and patients with stage 4 primary biliary cirrhosis. The natural history of HCC is variable, but it is often an aggressive tumor associated with poor survival without treatment. When diagnosed early, HCC may be amenable to potentially curative therapy. The three phases of pretherapy evaluation of HCC are detection, further evaluation of focal liver lesions, and staging. Detection often occurs in the setting of surveillance or in the use of periodic testing in people without HCC to identify lesions in the liver that are clinically suspicious for HCC. The evaluation phase involves the use of additional tests (radiological and/or histopathological) to confirm that a focal liver lesion is indeed HCC. Staging determines the extent and severity of a person's cancer to inform prognosis and treatment decisions. A number of staging systems are available, including the widely used TNM (tumor, node, metastasis) staging system and the more recent Barcelona Clinic Liver Cancer (BCLC) staging system, which has become the de facto staging reference standard; the Milan criteria have been used to identify patients likely to experience better post-transplantation outcomes, although other methods have been proposed. A number of imaging techniques are available to detect the presence of lesions, evaluate focal liver lesions, and determine the stage of the disease. They include ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Understanding the diagnostic accuracy of imaging methods and how they affect clinical decisionmaking, and ultimately patient outcomes, is a challenge. Imaging techniques may be used alone, in various combinations or algorithms, and/or with liver-specific biomarkers, resulting in many potential comparisons. Technical aspects of imaging methods are complex, and they are continuously evolving. Accurate diagnosis and staging of HCC are critical for providing optimal patient care. However, clinical uncertainty remains regarding optimal imaging strategies due to the factors described above. The purpose of this report is to comprehensively review the comparative effectiveness and diagnostic performance of different imaging modalities and strategies for detection of HCC, evaluation of focal liver lesions to identify HCC, and staging of HCC.