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Myelopathy is commonly encountered in clinical practice and is associated with a large number of causes. This article reviews the anatomy of the spinal cord and discusses how the clinical findings, time course, and radiographic patterns can help to identify the causes of myelopathy.Imaging observations such as MRI “pancake” gadolinium enhancement pattern with spondylotic myelopathy and subpial enhancement with neurosarcoidosis have improved diagnostic specificity. On the other hand, common diseases such as degenerative spine disease are now recognized as presenting much more variably. Improved imaging and the identification of genetic markers enhance the specificity of diagnosis. The improved identification of biomarkers has shown that the same cause, such as compressive myelopathy, can present more variably than previously appreciated.Spinal cord dysfunction, or myelopathy, remains a clinical diagnosis, and determining the cause requires integration of clinical, laboratory, and imaging parameters, none of which have great specificity individually. Most cases of myelopathy will require further neuroimaging, and some require CSF analysis for diagnosis. This article presents an approach to the diagnosis of myelopathy based on excluding compressive myelopathy initially and then differentiating between acute and subacute processes and chronic causes.