Chemical ablation with absolute ethanol is the most established technique of imaging-guided regional therapy for small hepatocellular carcinomas (HCCs), with long-term survival rates that rival those of surgical resection. In this article, the authors review patient selection criteria, techniques (including the one-shot approach of ethanol ablation for HCCs larger than 3 cm), complications, follow-up, and outcomes. The use of agents other than ethanol and the combination of chemical ablation with chemoembolization is also discussed.