The technological advances in molecular neuropharmacology and structural biology and the potential of large molecule therapeutics increase the number of potential drug targets and the ways in which these targets can be addressed to design novel therapeutic agents for CNS disorders. The target class approach has generated a large number of potential targets. Considerable progress has been made in exploiting an understanding of disease pathophysiology to identify novel targets for the treatment of neurodegenerative disorders. During the drug discovery process, target validation can be performed initially using in vitro or in vivo models but ultimately relies on demonstrating a clinical effect in patients. In Alzheimer's disease, two approaches to animal modeling are of interest: disease modification and cognition enhancement. An effective interface between basic research into disease mechanisms and the identification and validation of targets of interest to pre-clinical drug development is one of the key challenges.