ABSTRACT The concept of the immunological privilege of the central nervous system (CNS) has had a profound influence on studies of interactions between the immune system and the CNS. At one time there was considerable debate as to whether there were any cells in the CNS of myeloid origin, but we now know that there are a number of populations of myeloid cells in specialized compartments of the CNS and that there is an ongoing bidirectional dialogue between the CNS and the immune system. We briefly review what we know of the different myeloid populations, in particular the microglia: their phenotype and function; their role in CNS homeostasis; and also their role in pathology, focusing on chronic neurodegeneration.