GD3 ganglioside is a major glycolipid component of the developing central nervous system but diminishes considerably as the CNS matures. Despite consistent biochemical data, the cellular localization of GD3 expression has been controversial. In this commentary we will review the cellular expression of GD3 during CNS development and in neuropathological circumstances as determined by studies with the two most commonly used anti GD3 monoclonal antibodies, R24 and LB1. GD3 is not restricted to any one cell lineage, being expressed in development to varying degrees by immature neuroectodermal cells, oligodendrocyte progenitors, ameboid microglia, and subpopulations of developing neurons and astrocytes. In the adult CNS, GD3 is expressed in low amounts by some neuronal subpopulations, on reactive and resting microglia, and by reactive astrocytes. In the appropriate contexts of development or neuropathology, anti-GD3 antibodies are useful for cell type identification and for cell isolation, but caution should be exercised because of the lack of cellular specificity.