Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer death in the United States. The field of liver cancer is evolving rapidly with the emergence of new therapies, the potential for combining local and systemic therapies, and a better understanding of the molecular pathways that drive the development of liver cancer. HCC is a heterogenous cancer, most often arising in a diseased organ, with a dizzying array of potential therapies that depend upon liver function, burden of tumor, and institutional expertise. Unlike other cancers, the diagnosis can be made by dynamic imaging alone, and it is the only solid organ tumor for which transplant offers a cure. The management of HCC involves: a thorough understanding of the severity of the patient’s underlying liver disease; the benefits, risks, limitations, and sometimes trade-offs of potentially curative, bridging, and palliative therapies; and the role of the many specialties involved in treating HCC. Proper patient selection and multidisciplinary cooperation are essential to arrive at a rational plan of care for each patient and to achieve the best outcomes. A multidisciplinary conference or tumor board provides a forum wherein specialists can engage in patient selection, match the patient to the appropriate therapy, and consider patients for enrollment in clinical trials. When there is controversy or no clear evidence-based guidance, productive multidisciplinary teams will reach consensus and can often revisit challenging cases along the continuum of care.