Polymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modified for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood-brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications.