Microglia are the immunocompetent cells of the central nervous system. They respond with a process termed 'microglial activation' to any type of pathologic event. But also under normal conditions microglial cells are highly active by constantly screening their environment with their processes. Studies over the last years have established that microgilal cells express a variety of different purinergic receptors and we and others have established that these receptors are functional both in cell culture as well as in situ. Purinergic receptors control a variety of different microglial functions such as cytokine release, phagocytosis and migration. Interestingly, microglial cells express selectively defined ATP degrading enzymes namely and CD39 and CD73 which were originally used as microglial cell markes. We could establish that these enzymes modulate purinergic signaling and have an impact on microlgial migration and phagocytosis. Thus, purinergic signaling is complex and ATP has emerged as important signal to control microglial function.