Spinal cord injury (SCI) constitutes a profound central nervous system disorder characterized by significant neurological dysfunction and sensory loss below the injury site. SCI elicits a multifaceted cellular response in which the proliferation of reactive astrocytes and the ensuing diversity in their functions and phenotypes play pivotal roles within the injury microenvironment, especially during the secondary phases of the condition. This review explores the activation and heterogeneity of astrocytes following SCI. It underscores the necessity of delineating the heterogeneity among reactive astrocyte subpopulations throughout the secondary injury phase of SCI. Developing therapeutic strategies that capitalize on the beneficial properties of certain reactive astrocyte subpopulations while mitigating the adverse effects of others could have profound implications for future clinical management of SCI.