Alzheimer's disease (AD) is the multifarious progressive neuro-degeneration related dementia state among the elders. In fact, number of drugs with different mechanistic prospective were clinically developed and currently under R & D for the symptomatic treatment as well as disease-modifying management of AD. Unluckily, effective and safe delivery of drug in Alzheimer's is restricted due to the presence of biological as well as physiological barriers like blood–brain barrier (BBB), blood– cerebrospinal fluid barrier (BCSFB) and p-glycoproteins. Advancement in nanotechnology based drug delivery systems over the last decade exemplifies effective brain targeting by delivering the drugs at a constant rate that can be extended even up to months. Till recently, various nanomedicines such as polymeric and metallic nanoparticles, SLN, liposomes, micelles dendrimers, nanoemulsions and carbon nano-tube etc have been investigated for effective brain targeting of the drugs particularly in the treatment and diagnosis of AD. Here in this review, we given an account of different barrier in brain drug delivery and possible nanotechnology based strategies that can deliver drugs across the CNS barriers in AD. In addition, we illustrate the typical and new cholinesterase inhibitors for the management of AD, its clinical relevance and the challenges associated with their bioavailable brain delivery. Success of nanomedicines in effective therapeutic targeting in CNS with reference to literatures including the nanomedicines as the novel carrier of cholinesterase inhibitors anti-AD has also covered.