The field of long-circulating microparticulate drug carriers is reviewed. The protective effect of certain polymers including poly(ethylene glycol) on nanoparticulate carriers (liposomes, nanoparticles, micelles) is considered in terms of statistical behaviour of macromolecules in solution. Using liposomes as an example, the mechanism is discussed assuming that surface-grafted chains of flexible and hydrophilic polymers form dense ＇conformational clouds＇ preventing other macromolecules from interaction with the surface even at low concentrations of the protecting polymer. The scale of the protective effect is interpreted as the balance between the energy of the hydrophobic anchor interaction with the liposome membrane core or with the particle surface and the energy of the polymer chain free motion in solution. The possibility of using protecting polymers other than poly(ethylene glycol) is analysed, and examples of such polymers are given, based on polymer-coated liposome biodistribution data. General requirements for protecting polymers are formulated. Sterically protected nanoparticles and micelles are considered, and differences in steric protection of liposomes and particles are discussed. The problem of the preparation of drug carriers combining longevity and targetability is analysed. The biological consequences of steric protection of drug carriers with surface-grafted polymers are discussed, and possible clinical applications for long-circulating pharmaceutical carriers are considered.