Reactive astrocytosis occurs prominently in response to all forms of CNS injury or disease. The functions of reactive astrocytes are not well understood, and both harmful and beneficial activities have been attributed to these cells. The basic process of reactive astrocytosis is conserved in vertebrate evolution, suggesting fitness-enhancing benefits, but scar-forming reactive astrocytes are often regarded as uniformly detrimental to clinical outcome, in particular, when implicated as inhibitors of axon regeneration. Transgenic mouse models are providing new means to study the activities of reactive astrocytes after CNS insults in vivo. Recent studies point toward roles for reactive astrocytes in restricting inflammation and protecting neurons and oligodendrocytes, thereby helping to limit tissue degeneration and preserve function after CNS injury.