Brain diseases are a mayor public health concern worldwide. The blood-brain-barrier (BBB) acts as a protective shield, preventing the direct exposure of the central nervous system (CNS) to pathogens and toxic substances. While keeping the homeostatic environment of the brain, the BBB also prevents delivery of therapeutic substances. Therefore, it becomes an obstacle to treat many brain diseases. This limitation becomes more critical with the shift in therapeutics from small molecules to macromolecules. On the other hand, the BBB counts with several transport mechanisms for endogenous substances to satisfy the high metabolic requirements of the brain. Nanotechnology-based drug delivery strategies have become an opportunity to take advantage of those mechanisms and target the CNS without compromising the BBB structure or functionality. The modification of lipid nanoparticles (LNP) and other nanocarriers with surface moieties such as antibodies or peptides allows the stimulation and exploitation of transport mechanisms expressed in BBB. A systematic review was carried out to compile the functionalization strategies used in academic works, and to evaluate which studies have provided more evidence on the effectiveness of brain targeting. This is part of a research project that aims to deliver small interfering ribonucleic acid (siRNA) through the BBB, with LNP.