Astrocytes are specialized glial cells that outnumber neurons by over fivefold and are found throughout the central nervous system (CNS). They perform essential functions in the healthy CNS and respond to all forms of CNS insults through reactive astrogliosis, a process that has become a hallmark of CNS structural lesions. Recent research has advanced understanding of the functions and mechanisms of reactive astrogliosis and the roles of astrocytes in CNS disorders. Reactive astrocytes have a vast molecular arsenal and are involved in various clinicopathological entities. Reactive astrogliosis is not a simple all-or-none phenomenon but a finely graded continuum of changes regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy to long-lasting scar formation with tissue structure rearrangement. Evidence suggests that reactive astrogliosis may play either primary or contributing roles in CNS disorders through loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions. Astrocytes are divided into two main subtypes, protoplasmic and fibrous, based on their morphology and anatomical location. Protoplasmic astrocytes are found in gray matter and have a morphology of several stem branches that give rise to many finely branching processes. Fibrous astrocytes are found in white matter and have a morphology of many long fiber-like processes. Astrocytes make extensive contacts with blood vessels and have various functional interactions. GFAP is a prototypical marker for immunohistochemical identification of astrocytes. However, GFAP is not an absolute marker of all non-reactive astrocytes and is often not detectable in healthy CNS tissue or remote from CNS lesions. GFAP is expressed in many astrocytes throughout the healthy CNS, but many mature astrocytes in healthy CNS tissue do not express detectable levels of GFAP. GFAP is one of a family of intermediate filament proteins, including vimentin, nestin, and others, that serve largely cyto-architectural functions. Studies in transgenic mice indicate that GFAP expression is not essential for the normal appearance and function of most astrocytes in healthy CNS of transgenic mice, but is essential for the process of reactive astrogliosis and glial scar formation. Astrocytes play important roles in synaptic transmission, synaptic function, and synaptic plasticity. They express potassium and sodium channels and can exhibit evoked inward currents, but unlike neurons, astrocytes do not 'fire' or propagate action potentials along their processes. However, astrocytes exhibit regulated increases in intracellular calcium concentration that represent a form of astrocyte excitability. These regulated increases in astrocyte [Ca²+]iAstrocytes are specialized glial cells that outnumber neurons by over fivefold and are found throughout the central nervous system (CNS). They perform essential functions in the healthy CNS and respond to all forms of CNS insults through reactive astrogliosis, a process that has become a hallmark of CNS structural lesions. Recent research has advanced understanding of the functions and mechanisms of reactive astrogliosis and the roles of astrocytes in CNS disorders. Reactive astrocytes have a vast molecular arsenal and are involved in various clinicopathological entities. Reactive astrogliosis is not a simple all-or-none phenomenon but a finely graded continuum of changes regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy to long-lasting scar formation with tissue structure rearrangement. Evidence suggests that reactive astrogliosis may play either primary or contributing roles in CNS disorders through loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions. Astrocytes are divided into two main subtypes, protoplasmic and fibrous, based on their morphology and anatomical location. Protoplasmic astrocytes are found in gray matter and have a morphology of several stem branches that give rise to many finely branching processes. Fibrous astrocytes are found in white matter and have a morphology of many long fiber-like processes. Astrocytes make extensive contacts with blood vessels and have various functional interactions. GFAP is a prototypical marker for immunohistochemical identification of astrocytes. However, GFAP is not an absolute marker of all non-reactive astrocytes and is often not detectable in healthy CNS tissue or remote from CNS lesions. GFAP is expressed in many astrocytes throughout the healthy CNS, but many mature astrocytes in healthy CNS tissue do not express detectable levels of GFAP. GFAP is one of a family of intermediate filament proteins, including vimentin, nestin, and others, that serve largely cyto-architectural functions. Studies in transgenic mice indicate that GFAP expression is not essential for the normal appearance and function of most astrocytes in healthy CNS of transgenic mice, but is essential for the process of reactive astrogliosis and glial scar formation. Astrocytes play important roles in synaptic transmission, synaptic function, and synaptic plasticity. They express potassium and sodium channels and can exhibit evoked inward currents, but unlike neurons, astrocytes do not 'fire' or propagate action potentials along their processes. However, astrocytes exhibit regulated increases in intracellular calcium concentration that represent a form of astrocyte excitability. These regulated increases in astrocyte [Ca²+]i