Nanobiotechnology has been demonstrated to be an efficient tool for targeted therapy as well as diagnosis, with particular emphasis on brain tumor and neurodegenerative diseases. On this regard, the aim of this chapter is focused on engineered nanoparticles targeted to the brain, so that they have the ability to overcome the blood-brain barrier (BBB) and enter the brain tissue. Firstly, it highlighted the difficulty of physically active molecules and colloidal carriers to overcome BBB, which is an impediment for the treatment of several brain diseases; then, the use of nanoparticles as advantageous carriers to cross the BBB and achieve brain, and their functionalization strategies are described; and finally the delivery of nanoparticles to the target moiety, as diagnostics or therapeutics. Therefore, this chapter is focused on how the nanoparticle surface may be functionalized for drug delivery and diagnostics. Furthermore, it is also mentioned that some BBB targets were already used as transport mediators to central nervous system by functionalization on nanoparticles. It summarizes the nanoparticles potential in therapeutics and molecular targeting to BBB, and also an approach of the nanoparticle-mediated drug transport across the BBB, where nanoparticles take advantage of physiological receptor-mediated transport processes.