Blood-brain barrier (BBB) together with enzymes restricts the entry of substances for maintaining the internal milieu of the brain. Because of the presence of multiple endogenous transporters, BBB allows a selective entry of nutrients and minerals across it and limits the entry of foreign substances like drugs as well as neuropharmaceutical agents. This makes the CNS treatment ineffective. The conventional drug delivery systems which release drug into general circulation fail to deliver drugs effectively to brain and is therefore not very useful in treating certain diseases that affect CNS including Alzheimer's disease, dementia, Parkinson's disease, mood disorder, AIDS, viral and bacterial meningitis. Therefore there is a need to develop and design approaches which specifically target to brain in a better and effective way. The present review enlightens about several novel approaches including nanotechnology based approach like nanoparticles, liposomes, antibody mediated delivery approach and application of genomics in brain drug targeting that would give an insight to the researchers, academia and industrialists.