This review explores the concept of microglial activation states, particularly focusing on the M2 polarization as a potential therapeutic target in neurodegenerative diseases. Microglia, the resident immune cells of the central nervous system (CNS), can exist in multiple activation states, including classical (M1) and alternative (M2) activation. M1 microglia are characterized by pro-inflammatory cytokine production and reactive oxygen species (ROS) release, while M2 microglia exhibit anti-inflammatory and repair functions. The review highlights the importance of M2 microglia in acute and chronic neuroinflammation, such as spinal cord injury, traumatic brain injury, and stroke, where they play a crucial role in wound repair and reducing inflammation. In chronic neuroinflammation, such as multiple sclerosis and Alzheimer's disease, the balance between M1 and M2 microglia is critical. Altered microglial activation states can lead to disease progression, and therapeutic interventions aimed at inducing M2 polarization have shown promise in animal models and human studies. However, the complex nature of microglial activation and the potential for M2 cells to become less functional over time or under certain conditions remains a topic of ongoing research. The review concludes by emphasizing the need for a nuanced understanding of microglial activation states and their role in CNS diseases, suggesting that M2 polarization may not always be beneficial and that the environment plays a significant role in determining the functional state of microglia.This review explores the concept of microglial activation states, particularly focusing on the M2 polarization as a potential therapeutic target in neurodegenerative diseases. Microglia, the resident immune cells of the central nervous system (CNS), can exist in multiple activation states, including classical (M1) and alternative (M2) activation. M1 microglia are characterized by pro-inflammatory cytokine production and reactive oxygen species (ROS) release, while M2 microglia exhibit anti-inflammatory and repair functions. The review highlights the importance of M2 microglia in acute and chronic neuroinflammation, such as spinal cord injury, traumatic brain injury, and stroke, where they play a crucial role in wound repair and reducing inflammation. In chronic neuroinflammation, such as multiple sclerosis and Alzheimer's disease, the balance between M1 and M2 microglia is critical. Altered microglial activation states can lead to disease progression, and therapeutic interventions aimed at inducing M2 polarization have shown promise in animal models and human studies. However, the complex nature of microglial activation and the potential for M2 cells to become less functional over time or under certain conditions remains a topic of ongoing research. The review concludes by emphasizing the need for a nuanced understanding of microglial activation states and their role in CNS diseases, suggesting that M2 polarization may not always be beneficial and that the environment plays a significant role in determining the functional state of microglia.