As is readily apparent, both systems of drug administration have their advantages and disadvantages. Therefore, to obtain the most suitable nanosized drug delivery system, it is necessary to develop new structures that combine the good aspects of both systems. The lipid-polymer hybrid nanoparticle systems (CSHNs) that are the subject of this article have been developed within such a rational framework; by definition, they are core-shell hybrid systems that combine the mechanical advantages of biodegradable polymer-based nanocarriers and the biomimetic advantages of liposomes in a stable delivery system. Structurally, these hybrid nanoparticles consist of a single or multiple lipid layers surrounding a biodegradable polymer core (see Figure for the structures of hybrid core-shell drug delivery systems).