This review begins by attempting to recount some of the pioneering discoveries that first identified the presence of gangliosides in the nervous system, their structures and topography. This is presented as prelude to the current emphasis on physiological function, about which much has been learned but still remains to be elucidated. These areas include ganglioside roles in nervous system development including stem cell biology, membranes and organelles within neurons and glia, ion transport mechanisms, receptor modulation including neurotrophic factor receptors, and importantly the pathophysiological role of ganglioside aberrations in neurodegenerative disorders. This relates to their potential as therapeutic agents, especially in those conditions characterized by deficiency of one or more specific gangliosides. Finally we attempt to speculate on future directions ganglioside research is likely to take so as to capitalize on the impressive progress to date.