Intra nasal drug delivery system (INDDS) has emerged as a noninvasive alternative for delivering peptides, proteins and other therapeutic agents, specifically to CNS (Central nervous system). This route is well suitable for systemic delivery because of high vasculature, permeability, elimination of hepatic first pass metabolism and low enzymatic environment of the nasal cavity. This route of delivery is especially suited to treat CNS disorders like -neurodegenerative diseases, mood disorders, cognitive dysfunctioning etc., due to drugs ability to directly reach the brain by passing blood brain barrier (BBB). It is also a well suited delivery route for the biotechnological products like DNA plasmids, hormone, proteins, peptides, DNA vaccines to give enhanced bioavailability. A wide variety of therapeutic compounds may be administered intra-nasally for topical, systemic and CNS disorders. In this review, we have focussed on the nasal passage anatomical pathway leading to CNS drug delivery, different factors affecting nasal absorption, bioavailability barriers, vaccines and other therapeutic, biologically active molecules delivered via intra nasal route and strategies to improve nasal absorption. We have also outlined various in vitro and in vivo cellular models for nasal drug absorption and permeability studies.