In contrast to dendrimers, hyperbranched polymers show no distinguishable interior and periphery. Hyperbranched polyglycerol, however, possesses two types of OH functionalities (arising from linear and terminal glycerol units), which can be chemically differentiated. To generate a core-shell-type architecture in hyperbranched polyglycerol (M-n = 5000, M-w/M-n = 1.5), the 1,2-diols of the terminal glycerol units have been selectively converted into the corresponding acetals or ketals. This allows one to distinguish between interior (closer to the focal unit) and periphery (distant from the focal unit) of the macromolecule, since the remaining linear glycerol units remain unaffected by this transformation. In subsequent reactions, the linear units were functionalized with alkyl halides, such as allyl chloride or benzyl chloride, under phase transfer conditions to obtain the corresponding polyether polyketals. Selective deprotection of the 1,2-ketals was achieved with an acidic ion-exchange resin to give "core"-functionalized polyglycerols. By this procedure, hyperbranched polymers can be selectively tailored to contain hydrophobic substituents in the interior or in the periphery. Distribution coefficients (CHCl3/H2O), unusual thermal behavior, and spectroscopic properties of these macromolecules corroborate their core-shell-type architectures. Structural inversion of the architecture (apolar periphery with polar core vs polar periphery with apolar core) leads to striking changes in physical properties. Furthermore, the presented synthetic methods permit the preparation of a fully alkylated polyglycerol, which was obtained by phase transfer alkylation of polyglycerol. To demonstrate that the linear "core" units of polygylcerol are suitable for further selective functionalization, a polyglycerol pseudo-dendrimer, containing exclusively dendritic and terminal units, has been prepared by selective transformation of all linear into dendritic units.