This review discusses the challenges and advancements in brain-targeted drug delivery, particularly focusing on the use of targeting ligands in nanoparticles to overcome the blood-brain barrier (BBB) and deliver therapies specifically to brain cells. The BBB, characterized by tight junctions and a high electrical resistance, poses significant barriers to drug delivery to the brain. Nanoparticles (NPs) loaded with targeting ligands can enhance the delivery of drugs to specific brain cells, such as neurons, astrocytes, oligodendrocytes, microglia, and neural stem cells. Various types of targeting ligands, including peptides, proteins, aptamers, small molecules, and antibodies, are discussed, along with their effectiveness in directing NPs to specific cell types. The review highlights the advantages and limitations of this approach, emphasizing the need for further development to improve brain targeting and reduce off-target effects. Examples of successful applications of brain-targeted NPs in treating neurodegenerative diseases and brain tumors are provided, along with the challenges and future directions in this field.This review discusses the challenges and advancements in brain-targeted drug delivery, particularly focusing on the use of targeting ligands in nanoparticles to overcome the blood-brain barrier (BBB) and deliver therapies specifically to brain cells. The BBB, characterized by tight junctions and a high electrical resistance, poses significant barriers to drug delivery to the brain. Nanoparticles (NPs) loaded with targeting ligands can enhance the delivery of drugs to specific brain cells, such as neurons, astrocytes, oligodendrocytes, microglia, and neural stem cells. Various types of targeting ligands, including peptides, proteins, aptamers, small molecules, and antibodies, are discussed, along with their effectiveness in directing NPs to specific cell types. The review highlights the advantages and limitations of this approach, emphasizing the need for further development to improve brain targeting and reduce off-target effects. Examples of successful applications of brain-targeted NPs in treating neurodegenerative diseases and brain tumors are provided, along with the challenges and future directions in this field.