Rasmussen’s encephalitis (RE) is a rare neurologic disorder, with an incidence of 0.18 per 100,000 population, primarily affecting children, with an average onset at 6-7 years of age. Clinical manifestations include focal refractory epilepsy, progressive neurological deterioration, and cognitive decline. In imaging, magnetic resonance imaging (MRI) typically shows an increase in volume and sequences with T2/fluid-attenuated inversion recovery (FLAIR) signal, followed by atrophy. Positron emission tomography (PET) demonstrates a decline in metabolism in one hemisphere. Pathologically, neuronal loss, perivascular lymphocytic cuffing, and small glial nodules are prominent, with 10% of cases exhibiting dual pathology, primarily cortical dysplasia. Functional hemispherectomy remains the only therapeutic option, albeit resulting in permanent motor and cognitive deficits. Immunomodulatory therapy provides only temporary relief. Currently, the etiology and pathogenesis of RE remain unclear, presenting three major challenges: early diagnosis before hemisphere atrophy and neurocognitive impairment, managing immune therapies targeting inflammation, and determining rehabilitation post-surgery to maximize neurological recovery. Emerging evidence suggests that alterations in the brain’s immune microenvironment play a pivotal role in disease progression. This article focuses on the immunopathological aspects of RE, elucidating the roles of T lymphocytes, small glial cells, and astrocytes in the development of RE.