Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. In high-risk populations, including those with hepatitis B or C or with cirrhosis, serum α-fetoprotein (AFP) and screening ultrasound have improved detection of resectable HCC. Treatment options, including surgical resection, for patients with HCC must be selected based on the number and size of hepatic tumors, underlying hepatic function, patient condition, and available resources. An approach, which has been summarized shows the corresponding treatment choices under given clinical circumstances. For cirrhotic patients with less than three tumor nodules of a size less than 3 cm or a solitary HCC less than 5 cm, liver transplantation offers long-term survival similar to that observed in patients transplanted for nonmalignant disease. Ablative treatment using either chemical or thermal techniques provides locally effective tumor destruction. Transcatheter arterial chemoembolization (TACE) is commonly used for palliation of unresectable tumors as well as an adjunct to surgical resection, treatment of tumors before transplant, and in conjunction with other ablative therapies in a multimodality approach. Regional approaches to chemotherapy have produced more encouraging results than systemic chemotherapy, although both remain ineffective for long-term tumor control. Several newer treatment modalities are under investigation, including gene therapy, tagged antibodies, isolated perfusion, and novel radiotherapy techniques.