Cells that express the NG2 chondroitin sulfate proteoglycan and platelet-derived growth factor receptor alpha (NG2 glia) are widespread in the adult human cerebral cortex and white matter and represent 10-15% of non-neuronal cells. The morphology and distribution of NG2 glia are similar to, but distinct from, both microglia and astrocytes. They are present as early as 17 weeks gestation and persist throughout life. NG2 glia can be detected in a variety of human central nervous system (CNS) diseases, of which multiple sclerosis is the best studied. NG2 glia show morphological changes in the presence of pathology and can show expression of the Ki-67 proliferation antigen. The antigenic profile and morphology of NG2 glia in human tissues are consistent with an oligodendrocyte progenitor function that has been well established in rodent models. Most antibodies to NG2 do not stain formalin-fixed paraffin-embedded tissues. Advances in our understanding of NG2 glia in human tissues will require the development of more robust markers for their detection in routinely processed human specimens.