Microglia are the prime innate immune cells of the central nervous system. They can transit from a (so-called) resting state under homeostatic conditions towards a pro-inflammatory activation state upon homeostatic disturbances. Under neurodegenerative conditions, microglia have been largely perceived as neurotoxic cells. It is now becoming clear that resting microglia are not inactive but that they serve house-keeping functions. Moreover, microglia activity is not limited to proinflammatory responses, but covers a spectrum of reactive profiles. Depending on the actual situation, activated microglia display specific effector functions supporting inflammation, tissue remodeling, synaptic plasticity and neurogenesis. Many of these functions not only relate to the current state of the local neural environment but also depend on previous experience. In this review, we address microglia functions with respect to determining factors, phenotypic presentations, adaptation to environmental signals and aging. Finally, we point out primary mechanisms of microglia activation, which may comprise therapeutic targets to control neuro-inflammatory and neurodegenerative activity.