Zinc (Zn2+) is the second most abundant necessary trace element in the human body, exerting a critical role in many physiological processes such as cellular proliferation, transcription, apoptosis, growth, immunity, and wound healing. It is an essential catalyst ion for many enzymes and transcription factors. The maintenance of Zn2+homeostasis is essential for the central nervous system, in which Zn2+is abundantly distributed and accumulates in presynaptic vesicles. Synaptic Zn2+is necessary for neural transmission, playing a pivotal role in neurogenesis, cognition, memory, and learning. Emerging data suggest that disruption of Zn2+homeostasis is associated with several central nervous system disorders including Alzheimer’s disease, depression, Parkinson’s disease, multiple sclerosis, schizophrenia, epilepsy, and traumatic brain injury. Here, we reviewed the correlation between Zn2+and these central nervous system disorders. The potential mechanisms were also included. We hope that this review can provide new clues for the prevention and treatment of nervous system disorders.