IMPORTANCE: Hepatocellular carcinoma (HCC) is the sixth most common malignancy and fourth leading cause of cancer-related death worldwide. Recent advances in systemic and locoregional therapies have led to changes in many guidelines regarding systemic therapy, as well as the possibility to downstage patients to undergo resection. This review examines the advances in surgical and medical therapies relative to multidisciplinary treatment strategies for HCC. OBSERVATIONS: HCC is a major health problem worldwide. The obesity epidemic has made nonalcoholic fatty liver disease a major risk factor for the development of HCC. Multiple societies, such as the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, the Asian Pacific Association for the Study of the Liver, and the National Comprehensive Cancer Network, provide guidelines for screening at-risk patients, as well as define staging systems to guide optimal treatment strategies. The Barcelona Clinic Liver Cancer staging system is widely accepted and has recently undergone updates with the introduction of new systemic therapies and stage migration. CONCLUSIONS AND RELEVANCE: The treatment of patients with HCC should involve a multidisciplinary approach with collaboration among surgeons, medical oncologists, radiation oncologists, and interventional radiologists to provide optimal care. Treatment paradigms must consider both tumor and patient-related factors such as extent of liver disease, which is a main driver of morbidity and mortality. The advent of more effective systemic and locoregional therapies has prolonged survival among patients with advanced disease and allowed some patients to undergo surgical intervention who would otherwise have disease considered unresectable.