Branched polyesters consisting of poly (vinyl alcohol) (PVA) grafted with chains of poly (lactic-co-glycolic acid) (PLGA) represent a new class of biodegradable polymers showing significant potential for the development of a variety of drug delivery vehicles. The amphiphilic character and the resulting increase in hydrophilicity of this class of polymers provide advantages when packaging sensitive drug molecules, such as proteins, peptides or DNA. Furthermore, the PVA backbone can be modified, for example, with sulfobutyl moieties or amine structures, to create polymers with negative or positive charges. The ability to modify not only the backbone but also the length of the PLGA side chains results in an extremely flexible polymer system, which can be adapted to meet the needs of almost any drug substance. Further, the rate of biodegradation may also be manipulated through polymer modification to achieve half-lives ranging from several hours to several weeks. This review provides an overview of the three major groups of branched polyesters based upon poly (vinyl alcohol)-grafted poly (lactic-co-glycolic acid) (PVA-g-PLGA), namely, the neutrally charged PVA-g-PLGA, the negatively charged sulfobutyl-modified PVA-g-PLGA and the positively charged amine-modified PVA-g-PLGA, as well as their use in various drug delivery systems.