Hyperhomocysteinemia (HHcy) is related to central nervous system diseases. Epidemiological studies show a positive, dose-dependent relationship between plasma total homocysteine (tHcy) concentration and neurodegenerative disease risk. tHcy is a marker of B-vitamin (folate, B-12, B-6) status. Hypomethylation, caused by low B-vitamin status and HHcy, is linked to key pathomechanisms of dementia; B-vitamin supplementation could potentially reduce neurological damage. In retrospective studies, the association between tHcy and cognition is impressive; there is also evidence that tHcy-lowering treatment could be effective in primary and secondary stroke prevention. Increased tHcy and low serum folate occur in patients with Parkinson's disease, especially those receiving L-dopa. There is also an association between HHcy and multiple sclerosis, and between B-vitamin status and depression. Studies also confirm a causal role for tHcy in epilepsy, and certain anti-epileptics enhance HHcy. B-vitamin status should be optimized by ensuring sufficient intake in patients with neuropsychiatric diseases. HHcy occurs commonly in the elderly and can contribute to age-related neurodegeneration. Treatment with folic acid, B-12 and B-6 lowers tHcy. For secondary and primary prevention from several neuropsychiatric disorders, it seems prudent to actively identify deficient subjects and ensure sufficient vitamin intake.