Astrocytes play crucial roles in the normal function of the CNS, including the regulation of synaptic activity, modulation of excitatory and inhibitory neurotransmission, support of energy metabolism, maintenance of extracellular pH and ion homeostasis, detoxification processes and maintenance of blood-brain barrier (BBB) integrity. Astrocytes are also key players in almost all pathological processes affecting the CNS. The aim of this chapter is to review normal and pathological properties of astrocytes, focusing on the signaling mechanisms involved in the formation of reactive astrocytes and cell swelling. A fuller understanding of the signaling mechanisms involved in these responses may provide novel therapeutic targets for ameliorating the ravages brought about by neurologic disease.