There is an increasing awareness that the astrocytes in the immature periventricular white matter are vulnerable to ischemia and respond to inflammation. Here we provide a synopsis of the articles that have evaluated the causes and consequences of developmental brain injuries to white matter astrocytes as well as the consequences of several genetic mutations that result in abnormal astrocyte development. Emerging data suggest that the astrocytes are not simply responding to the injury but are likely victims as well as culprits. Given the important roles that astrocytes play in maintaining ionic, neurotransmitter, and metabolic homeostasis in the brain, a more thorough understanding of the mechanisms that lead to their incapacitation, demise, or reactions as well as a better understanding of the stimuli that regulate their neuroprotective and regenerative properties will enable these cells to be manipulated to preserve the integrity of white matter and to potentially provide therapeutics to enhance neonatal regeneration and recovery from brain injury.