Transarterial radioembolization (TARE) using Yttrium-90 (Y-90) microspheres is emerging as a mainstream treatment modality in the management of patients with primary and metastatic liver cancer. Yttrium-90 is a high energy beta particle emitting radioisotope. The intellectual basis of Y-90 microsphere treatment is the preferential distribution of microspheres, when injected in the hepatic artery, yielding much higher concentrations in the tumor compartment than the normal liver parenchyma. The technique involves the administration of Y-90 microspheres into the hepatic artery accessed via transfemoral route, showing almost similar procedure with transarterial chemoembolization (TACE). The Y-90 microspheres are entrapped within the microvasculature, and release beta radiation. The high tumor to liver concentration ratio results in an effective tumoricidal radiation absorbed dose whilst limiting the radiation injury to the normal liver. With such a therapeutic mechanism of this method, Y-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. But preliminary evidence also suggests that the TACE and TARE provided similar effectiveness and toxicity in patients with unresectable HCC. In conclusion, we think that prospective, randomized controlled trials using current therapies are needed to better define optimal management of unresectable HCC.