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Myelopathy may occur as a consequence of various metabolic and toxic conditions. This article provides an update on the clinical presentations, diagnostic evaluations, and management of metabolic and toxic myelopathies.Myelopathy and myeloneuropathy due to vitamin B12 deficiency is increasing in prevalence partly because of an aging population. Early recognition of the clinical symptoms and rapid initiation of treatment is essential. Copper deficiency is now also recognized as causing a similar clinical picture as vitamin B12 deficiency. Conditions leading to copper deficiency include bariatric surgery and excessive zinc intake. Unusual conditions such as lathyrism and konzo are relevant to all neurologists because of emigration from less well-developed countries. Myelopathy can also occur from substance abuse (eg, heroin and nitrous oxide), and early diagnosis could lead to improved patient outcomes. The spinal cord may also be injured in decompression illness that occurs in sport divers and individuals who work in pressurized atmospheres.Knowledge and recognition of the various metabolic and toxic causes of myelopathy is important for the practicing neurologist, as timely diagnosis and rapid initiation of therapy is essential to improve the chances for recovery.