Microglia are essential for the development and function of the adult brain. Their ontogeny, together with the absence of turnover from the periphery and the singular environment of the central nervous system (CNS), make microglia a unique cell population compared to other tissue-macrophages. The unique properties and functions of microglial cells, such as their role in synaptic pruning or the exceptional capacity to scan the brain parenchyma and rapidly react to its perturbations, have emerged in recent years. In the coming years, understanding how microglia acquire and maintain their unique profiles in order to fulfil distinct tasks in the healthy CNS and how these are altered in disease, will be essential to develop strategies to diagnose or treat CNS disorders with an immunological component. Frontiers in Immunology 3 September 2018 | Microglia in Health and Disease This Research Topic covers several aspects of microglial biology, ranging from their origin and the functional role of microglia during development and lifespan, their molecular properties compared with other brain and peripheral immune cells to microglial phenotypes and functional states in neurodegenerative diseases and brain tumours. In conclusion, the present Research Topic provides a comprehensive overview of our current understanding of several cellular and molecular mechanisms that make microglia a unique immune cell population within the healthy CNS as well as under inflammatory, neurodegenerative and tumorigenic processes.