Worldwide, hepatocellular carcinoma (HCC) is a common, refractory, malignant tumor. Surgical resection is feasible in only a few patients, because of limited hepatic reserve and multifocality of tumors at diagnosis. Percutaneous ablation therapies, including injection of ethanol (PEI) or acetic acid (PAI), radiofrequency ablation (RFA), and microwave coagulation therapy (MCT), have been the major treatments for unresectable HCC in the past decade. PEI is well established for small (< 3 cm) HCC, and PAI is equally as effective as PEI, but with fewer treatment sessions. RFA has recently been suggested to have excellent tumor-ablating ability because it produces a fixed and predictable tumor necrosis zone. Although RFA is also effective for medium-sized HCC, the overall complication rate may be higher than previously assumed. MCT is similar to RFA in its clinical application and potential adverse effects. A combination approach using percutaneous ablation therapy and transcatheter arterial embolization was shown to be effective for large HCC. Other approaches, such as injection of hot saline or yttrium-90 microspheres, cryoablation, or interstitial laser photocoagulation, are less often used nowadays. Multimodal, image-guided, tailored therapy, rather than a fixed treatment algorithm, might be more practical for unresectable HCC. In conclusion, although longterm survival is possible in selected patients with HCC, the overall prognosis remains suboptimal, especially in patients with unfavorable tumor characteristics. While newer anti-tumor therapies with improved efficacy are needed, information about a more rational approach to the use of existing therapeutic options may help to enhance treatment strategies for HCC.