High-intensity focused ultrasound (HIFU) is becoming an increasingly attractive modality for ablation. Enhancement of HIFU is an important issue that has been discussed and investigated worldwide. Ultrasound contrast agents are considered to constitute an efficient medium for changing acoustic characteristics and improving energy deposition in the focal region. The role of microbubbles in inducing enhanced heating, cavitation, and other related events in HIFU ablation has been investigated, with the goal of improving coagulation necrosis volume or decreasing acoustic power and exposure duration. Consequently, with the use of ultrasound contrast agents, applications of HIFU are expected to become more efficient, safe, and accurate and to produce fewer adverse effects. This paper reviews studies that have been conducted to investigate the enhancement of ultrasound contrast agents in HIFU ablation through experiments that were carried out in vitro and in vivo; an analysis of results of this enhancement mechanism is provided.