From the viewpoint of safety, non-viral vector systems represent an attractive gene delivery system for gene therapy. However, the transfection efficiency of non-viral vectors in vivo is generally very low. Previously, it was reported that microbubbles, utilized as imaging agents for diagnostic echocardiography, could promote gene delivery into cells when combined with ultrasound exposure. We therefore developed novel liposomal bubbles (Bubble liposomes) containing the lipid nanobubbles of perfluoropropane which is used as ultrasound imaging agent. These Bubble liposomes were smaller in diameter than conventional microbubbles and induced cavitation upon exposure to ultrasound. These results suggested that cavitation of these Bubble liposomes could be an efficient approach for delivering plasmid DNA into cells. In addition, in in vivo gene delivery, the combination of Bubble liposomes and ultrasound provided more effective gene delivery than conventional lipofection methods, further suggesting that Bubble liposomes could be effective as a non-viral vector system in in vivo gene delivery. In this review, we discuss the characteristics of Bubble liposomes and their potential utility as a gene delivery tool in vitro and in vivo.