Understanding the complexities of the liver has been a long-standing challenge to physicians and anatomists. Significant strides in the understanding of hepatic anatomy have facilitated major progress in liver-directed therapies—surgical interventions, such as transplantation, hepatic resection, hepatic artery infusion pumps, and hepatic ablation, and interventional radiologic procedures, such as transarterial chemoembolization, selective internal radiation therapy, and portal vein embolization. Without understanding hepatic anatomy, such progressive interventions would not be feasible. This article reviews the history, general anatomy, and the classification schemes of liver anatomy and their relevance to liver-directed therapies.