Microglia are specialized immune cells in the central nervous system (CNS) that exhibit dynamic morphological changes in response to injury or infection. Their morphology is a key indicator of their functional state, though it is not synonymous with function. This review discusses how morphological changes in microglia can provide insights into their reactivity and function. It emphasizes the importance of combining histological and genetic approaches to fully understand microglial reactivity. Immunohistochemistry is a crucial tool for analyzing microglial morphology, as it allows for the visualization of specific markers such as Iba1, CX3CR1, and CSF-1R. Different morphological states of microglia, including ramified, ameboid, bushy, and rod-shaped, are associated with various functions and pathological conditions. The review also highlights the role of sex and circadian rhythms in influencing microglial morphology. Additionally, it discusses the use of advanced imaging techniques and machine learning to analyze microglial morphology in real-time. The review concludes that while microglial morphology is an important measure, it should be interpreted in the context of other functional markers and combined with histological and genetic approaches for a comprehensive understanding of microglial function and reactivity.Microglia are specialized immune cells in the central nervous system (CNS) that exhibit dynamic morphological changes in response to injury or infection. Their morphology is a key indicator of their functional state, though it is not synonymous with function. This review discusses how morphological changes in microglia can provide insights into their reactivity and function. It emphasizes the importance of combining histological and genetic approaches to fully understand microglial reactivity. Immunohistochemistry is a crucial tool for analyzing microglial morphology, as it allows for the visualization of specific markers such as Iba1, CX3CR1, and CSF-1R. Different morphological states of microglia, including ramified, ameboid, bushy, and rod-shaped, are associated with various functions and pathological conditions. The review also highlights the role of sex and circadian rhythms in influencing microglial morphology. Additionally, it discusses the use of advanced imaging techniques and machine learning to analyze microglial morphology in real-time. The review concludes that while microglial morphology is an important measure, it should be interpreted in the context of other functional markers and combined with histological and genetic approaches for a comprehensive understanding of microglial function and reactivity.