Hepatocellular carcinoma (HCC) is a complex disease with a poor prognosis. Incidence and mortality rates are increasing in many geographical regions, indicating a need for better management strategies. Among several risk factors for HCC, the most common are cirrhosis because of chronic hepatitis B virus or hepatitis C virus infection and alcohol consumption, obesity, and diabetes. In some patients, combined risk factors present additional challenges to the prevention and treatment of HCC. Screening and surveillance of high-risk populations varies widely by geographic regions, and access to optimal surveillance is critical for early diagnosis. The treatment choice for HCC depends on the cancer stage, patient performance status, and liver function and requires a multidisciplinary approach and close cooperation among specialists for the best patient outcomes. Despite advances in surgical treatments and locoregional therapies, recurrence and liver failure remain significant challenges. The pathogenesis of HCC is a multistep and complex process, wherein angiogenesis plays an important role. The multikinase inhibitor sorafenib is the only approved targeted agent for advanced HCC, although promising results have been obtained with other targeted agents and combinations, and the results of ongoing trials are eagerly awaited. Clinical trials with rigorous study designs, including molecular classification and validation of new molecular biomarkers, are required to improve the personalized treatment of HCC. This article provides an overview of HCC and was developed through a review of relevant literature, clinical trial data, and updated clinical guidelines.