: Radiotherapy is a common treatment for brain and spinal cord tumors and also a risk factor for brain neuropathological changes in different neurological and neuropsychological disorders. Astroglial connexins have been involved in the brain inflammation, development of Alzheimer’s disease (AD), depressive, epilepsy, and amyotrophic lateral sclerosis, and are affected by radiation exposure. Therefore, it is speculated that radiation-induced changes of astroglial connexins may be related to the brain neuropathology and development of neurological and neuropsychological disorders. In this paper, we reviewed the functional expression and regulation of astroglial connexins expressed between astrocytes and different types of brain cells (including oligodendrocytes, microglia, neurons and endothelial cells). The roles of these connexins in the development of AD, depressive, epilepsy, amyotrophic lateral sclerosis and brain inflammation were also summarized. The radiation-induced astroglial connexins changes and development of different neurological and neuropsychological disorders were then discussed. Based on currently available data, we proposed that radiation-induced astroglial connexins changes may be involved in the genesis of different neurological and neuropsychological disorders which depends on the age, brain regions, and radiation doses/dose rates. The abnormal astroglial connexins may be novel therapeutic targets for the prevention of radiation-induced cognitive impairment, neurological and neuropsychological disorders.