Liposomes have been investigated for use as drug carriers, and many previous studies have demonstrated enhanced efficacy of encapsulated drugs and the reduction of the side effects of drugs so entrapped. In many cases liposomal drugs are administered via the bloodstream. The stability in the bloodstream, clearance, and biodistribution are dependent on the composition, size, and charge of the liposomes. Rigid, small-size (100-200 nm) liposomes tend to be retained in the blood without degradation. Since the conventional liposomes are trapped in the reticuloendothelial system (RES), RES targeting by means of liposomes is easily achieved. This tendency of liposomes, however, is the most serious limitation when their target is not the RES. Many attempts have been made to avoid the RES-trapping and to prolong the circulation time of liposomes with monosialoganglioside GM1, polyethyleneglycol, glucuronide derivatives, and so on. When the targets are tumor tissues, these RES-avoiding, long-circulating liposomes passively accumulate in such tissues due to extravasation through the leaky vasculature in the tumor tissues. Therefore, long-circulating liposomes are useful tools, especially for tumor imaging and therapy. In this review, we show examples and discuss the mechanism of RES avoidance by these modifiers of liposomes, with special focus on the glucuronide as a modifier.