In the mammalian brain, olfaction is an important sense that is used to detect odors of different kinds that can warn of off food, to produce a mothering instinct in a flock or group of animals, and to warn of danger such as fire or poison. The olfactory system is made up of a long-distance rostral migratory stream that arises from the subventricular zone in the wall of the lateral ventricle, mainly comprises neuroblasts, and stretches all the way through the basal forebrain to terminate in the olfactory bulb. The olfactory bulb receives a constant supply of new neurons that allow ongoing integration of new and different smells, and these are integrated into either the granule cell layer or the periglomerular layer. The continuous turnover of neurons in the olfactory bulb allows us to study the proliferation, migration, and differentiation of neurons and their application in therapies for neurodegenerative diseases. In this chapter, we will examine the notion that the olfactory system might be the route of entry for factors that cause or contribute to neurodegeneration in the central nervous system. We will also discuss the enzymes that may be involved in the addition of polysialic acid to neural cell adhesion molecule, which is vital for allowing the neuroblasts to move through the rostral migratory stream. Finally, we will discuss a possible role of endosialidases for removing polysialic acid from neural cell adhesion molecules, which causes neuroblasts to stop migrating and terminally differentiate into olfactory bulb interneurons.