Reactive astrogliosis, a process where astrocytes undergo molecular and morphological changes in response to central nervous system (CNS) injuries or diseases, is a poorly understood but ubiquitous phenomenon. Recent genetic tools have enabled the molecular dissection of reactive astrogliosis in vivo, revealing that it can have both beneficial and detrimental effects, depending on the specific molecular signaling cascades involved. This article reviews recent advances in understanding the signaling mechanisms that regulate reactive astrogliosis and highlights the potential to identify novel therapeutic targets for neurological disorders. Reactive astrogliosis is not a single, all-or-none response but a spectrum of changes that vary in severity and context. Astrocytes produce a wide range of molecules and can exhibit both pro- and anti-inflammatory effects, depending on the signaling mechanisms involved. The article discusses the protective and repair functions of reactive astrocytes, such as uptake of excitotoxic glutamate, protection from oxidative stress, and regulation of blood-brain barrier function. However, dysfunctions or detrimental effects of reactive astrogliosis can contribute to CNS diseases, either by loss of normal functions or gain of abnormal effects. The article also explores the potential for therapeutic strategies that target specific aspects of reactive astrogliosis to enhance beneficial functions or attenuate detrimental effects.Reactive astrogliosis, a process where astrocytes undergo molecular and morphological changes in response to central nervous system (CNS) injuries or diseases, is a poorly understood but ubiquitous phenomenon. Recent genetic tools have enabled the molecular dissection of reactive astrogliosis in vivo, revealing that it can have both beneficial and detrimental effects, depending on the specific molecular signaling cascades involved. This article reviews recent advances in understanding the signaling mechanisms that regulate reactive astrogliosis and highlights the potential to identify novel therapeutic targets for neurological disorders. Reactive astrogliosis is not a single, all-or-none response but a spectrum of changes that vary in severity and context. Astrocytes produce a wide range of molecules and can exhibit both pro- and anti-inflammatory effects, depending on the signaling mechanisms involved. The article discusses the protective and repair functions of reactive astrocytes, such as uptake of excitotoxic glutamate, protection from oxidative stress, and regulation of blood-brain barrier function. However, dysfunctions or detrimental effects of reactive astrogliosis can contribute to CNS diseases, either by loss of normal functions or gain of abnormal effects. The article also explores the potential for therapeutic strategies that target specific aspects of reactive astrogliosis to enhance beneficial functions or attenuate detrimental effects.