The brain is the most lipid-rich organ in the body and, owing to the impermeable nature of the blood brain barrier, lipid and lipoprotein metabolism within this organ is distinct from the rest of the body. Apolipoproteins play a well-established role in the transport and metabolism of lipids within the CNS; however, evidence is emerging that they also fulfill a number of functions that extend beyond lipid transport and are critical for healthy brain function. The importance of apolipoproteins in brain physiology is highlighted by genetic studies, where apolipoprotein gene polymorphisms have been identified as risk factors for several neurological diseases. Furthermore, the expression of brain apolipoproteins is significantly altered in several brain disorders. The purpose of this article is to provide an up-to-date assessment of the major apolipoproteins found in the brain (ApoE, ApoJ, ApoD and ApoA-I), covering their proposed roles and the factors influencing their level of expression. Particular emphasis is placed on associations with neurological and psychiatric disorders.