Hepatocellular carcinoma (HCC) typically occurs in patients with advanced liver disease, so therapeutic decisions must account for the degree of underlying liver dysfunction and patient performance status in addition to tumor burden. Curative treatment options, including liver transplantation, surgical resection, and local ablative therapies, offer 5-year survival rates exceeding 60% but are restricted to patients with early-stage HCC. Surgical resection and local ablative therapies are also limited by high recurrence rates, highlighting a need for adjuvant and/or neoadjuvant therapies. A majority of patients with HCC are diagnosed beyond an early stage, when the tumor is no longer amenable to curative options. For patients with liver-localized HCC in whom curative options are not possible, transarterial therapies, either chemoembolization or radioembolization, can prolong survival but are rarely curative. Sorafenib and regorafenib are the only approved first-line and second-line systemic therapies, respectively, with a survival benefit for patients with advanced HCC; however, the benefit is primarily observed in patients with intact liver function and good performance status. There are several ongoing phase II and III trials evaluating novel systemic therapies, including immunotherapies. Patients with poor performance status or severe hepatic dysfunction do not derive any survival benefit from HCC-directed therapy and have a median survival of approximately 6 months. These patients should be treated with best supportive care, with a focus on maximizing quality of life. Multidisciplinary care has been shown to improve appropriateness of treatment decisions and overall survival and should be considered standard of care for patients with HCC.