One of the main challenges in brain drug distribution is the presence of blood-CNS barriers, which prevent the delivery of drugs to destination cells, such as neurons, astrocytes, or oligodendrocytes. The primary barriers to the central nervous system are the blood-brain and blood-cerebrospinal fluid barriers. It has been shown that the presence of specific membrane efflux transporters, including certain members of the ATP-binding cassette (ABC) transporter family, on the cells that make up the barriers plays a vital role in reduced drug accumulation in the brain. Studies of the expression and cellular localization of such proteins are the subject of interest for current neurological drug design. While the silencing of ABC transporters has been proven to improve the efficiency of treatment in several neurological disorders such as epilepsy, inducing the expression of ATP-binding cassette transporters can be targeted to reduce the unfavorable side effects of drugs to protect the neurons during the treatment process. The current review summarizes recent findings on the expression of these transporters in CNS focusing on MRP1-6, ABCB1, and ABCG2 proteins and their pharmacological significance in a variety of neurological disorders.