Microglial cells are the immune cells of the brain, but they also interact with the other intrinsic brain cells. Over the last years it has become evident that they are not only involved in pathological processes, but also in the healthy brain during development and plasticity. We have developed novel mouse lines to study the interaction of microglia during brain activity. We could show that microglia respond indirectly to synaptic activity via astrocytes. In addition we studied the involvement of microglia in different brain diseases. We found that there is a complex interaction of microglia with glioma cells which has a strong impact on tumor growth.