The concept of a brain microbiome has emerged as a dynamic area of research, challenging the long-held view of the brain as a sterile organ. This paradigm shift, enabled by sequencing and imaging technologies advancements, has revealed microbial DNA, RNA, and intact microorganisms within brain tissue. Early skepticism about these findings, rooted in the protective nature of the blood-brain barrier and the brain’s immune privilege, has given way to evidence suggesting a localized microbiome with potential roles in health and disease. Initial studies focused on identifying these microbes and investigating their origins, proposing mechanisms such as hematogenous dissemination or translocation from the gut via the vagus nerve. Research has uncovered associations between microbial signatures and neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and multiple sclerosis. As of 2025, the field is evolving to explore the functional implications of brain-resident microorganisms. Emerging studies highlight their potential to influence central nervous system processes, such as immune modulation, neurotransmitter synthesis, and neurogenesis. Evidence also suggests their involvement in neurodevelopment and psychiatric conditions, including depression and schizophrenia. These findings underscore the importance of the brain microbiome in shaping behavior and cognitive functions. Future research aims to unravel these microorganism’s origins, mechanisms, and therapeutic potential, promising novel interventions in neurology and psychiatry and redefining our understanding of brain health through a microbial lens.