Intranasal (i.n.) administration is a relatively novel technique to target therapeutics to the central nervous system for the treatment of neurodegenerative and other brain diseases. Rather than being released into the bloodstream, drugs administered i.n. gain direct access to the central nervous system by traveling extracellularly along the olfactory and trigeminal nerves, and via the perivascular space. The main benefits are that drugs bypass the blood–brain barrier, systemic exposure to the liver and other organs is minimal, and it is noninvasive. Several drugs in our laboratory have been delivered to rodent models of neurodegenerative disease and shown efficacy. Foremost is intranasal deferoxamine (i.n. DFO), which has shown efficacy in rodent models of Alzheimer and Parkinson diseases. In Alzheimer mouse models, i.n. DFO decreases spatial memory loss and soluble amyloid in both tau and amyloid models. In a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson disease, i.n. DFO decreased Parkinsonian symptoms in the drug-induced rotational and cylinder tests, and the magnitude of lesions in the medial forebrain bundle. Approval for i.n. DFO is currently being pursued for clinical trials. These studies demonstrate that i.n. administration also has potential for the treatment of Huntington disease (HD). Indeed, some studies presented at the most recent annual meeting of the Society for Neuroscience included IN treatments for rodent models of HD, and are likely to be published soon leading the way for i.n. administration of drugs for HD.