The application of polymers in medicine, as components of drug carriers, as well as their synthetic strategies are considered essential for producing and developing new drug formulations against human deceases. The synthesis of block copolymers is a timeconsuming process with a high cost of the final product, although several block copolymer systems have been already commercialized successfully. The biocompatibility, the biodegradability and the non toxic profile of newly synthesized polymers towards healthy tissues, should be taken into account in order to be acceptable for biomedical applications. In this review article, focus is placed on new approaches and synthetic strategies for preparing novel block copolymers and their utilization as parts of new and advanced Drug Delivery nanoSystems (aDDnSs) with a Modulatory Controlled Release profile (MCR). Such complex and advanced nanosystems can alter the pharmacokinetic properties of the encapsulated drug and consequently its effectiveness. Emphasis is given to the use of living polymerization methodologies and post polymerization chemical transformation reactions for the synthesis of mainly diblock copolymers for novel drug delivery nanosystems. Issues related to self-assembly of block copolymers in solution toward formation of colloidal functional nanostructures that can serve as nanocontainers and nanocarriers, and strategies for controlling encapsulation of specific drugs are also discussed. Specific examples are reported mainly on diblock copolymer systems, including authors’ recent work.