To make universal and efficient liposome‐based drug carriers, liposomes should be able to recognize and bind other targets beyond their natural targets, the cells of the reticuloendothial system. To make liposomes targeted, numerous methods to couple active substances, primarily, monoclonal antibodies, to the liposome surface have been developed. Resulting immunoliposomes (or affinity liposomes) demonstrate good targeting to cells and organs both in vitro and in vivo. However, the short circulation time of immunoliposomes prevented them from accumulating in targets with diminished blood flow or low antigen concentration. Long‐circulating liposomes were prepared by coupling soluble and flexible polymers, such as polyethylene glycol, to the liposome surface. The mechanism of liposome steric protection with flexible polymers is based on the formation of dense ‘conformational cloud’ by a grafted polymer over the liposome surface, and might be analyzed in terms of a statistical model of polymer solutions. By co‐immobilization of specific antibodies and protecting polymers on the liposome surface, liposomes can be prepared combining both targetability and prolonged circulation in vivo. A biological model (experimental myocardial infarction in rabbit) was used to estimate the relative importance of different factors (liposome size and coating with protective polymer and/or specific antibody) for effective accumulation of liposomes in the target. Statistical analysis demonstrated that different types of liposomes have to be used in order to reach maximum absolute delivery of liposomes to the target, or maximum target‐to‐non‐target ratio (relative delivery). Therefore, different liposomes should be used as carriers of diagnostic and therapeutic agents.