Mounting evidence is overturning the long-held dogma that antibodies enter the brain only through vascular leaks or blood–brain barrier disruption. Instead, neurons, astrocytes, and microglia themselves can generate restricted but functional immunoglobulin repertoires. This capacity arises through unconventional molecular processes including cryptic V(D)J recombination, splice-and-link RNA editing, and retroelement-assisted rearrangements. Far from being passive bystanders, these endogenous antibodies perform active and diverse roles within the central nervous system. At the synaptic level, neural immunoglobulins tag exuberant synapses for complement-mediated pruning, a mechanism crucial for development, circuit refinement, and adaptive plasticity. They also influence receptor recycling, thereby tuning neurotransmission and maintaining responsiveness to activity. In parallel, they regulate astrocyte–neuron metabolic coupling, ensuring a balanced distribution of energy substrates between cell types. Following injury, neural cells exhibit dynamic and cell-type-specific immunoglobulin class switching. Early waves of antibody expression tend to promote axonal extension and tissue regeneration, whereas later responses act to temper neuroinflammation and prevent runaway damage. Within astrocytes, IgG molecules appear to act as phenotype gatekeepers, dictating whether astrocytes maintain supportive functions or shift toward reactive, potentially pathological states. In disease contexts, this system reveals its double-edged nature. In neurodegenerative disorders or autoimmune conditions, neural immunoglobulins can mitigate pathology by buffering damage and restoring homeostasis. Yet in other circumstances, they exacerbate disease progression, amplifying immune-mediated injury. This paradox underscores their pivotal role in brain physiology and pathology, positioning them as both protectors and potential drivers of neural dysfunction.