The occurrence of acute myelopathy in a nontrauma setting constitutes a medical emergency for which spinal MRI is frequently ordered as the first step in the patient's workup. The emergency department radiologist should be familiar with the common differential diagnoses of acute myelopathy and be able to differentiate compressive from noncompressive causes. The degree of spinal cord compression and presence of an intramedullary T2-hyperintense signal suggestive of an acute cord edema are critical findings for subsequent urgent care such as surgical decompression. Importantly, a delay in diagnosis may lead to permanent disability. In the spinal canal, compressive myelopathy can be localized to the epidural, intradural extramedullary, or intramedullary anatomic spaces. Effacement of the epidural fat and the lesion's relation to the thecal sac help to distinguish an epidural lesion from an intradural lesion. Noncompressive myelopathy manifests as an intramedullary T2-hyperintense signal without an underlying mass and has a wide range of vascular, metabolic, inflammatory, infectious, and demyelinating causes with seemingly overlapping imaging appearances. The differential diagnosis can be refined by considering the location of the abnormal signal intensity within the cord, the longitudinal extent of the disease, and the clinical history and laboratory findings. Use of a compartmental spinal MRI approach in patients with suspected nontraumatic spinal cord injury helps to localize the abnormality to an epidural, intradural extramedullary, or intramedullary space, and when combined with clinical and laboratory findings, aids in refining the diagnosis and determining the appropriate surgical or nonsurgical management.Online supplemental material is available for this article.©RSNA, 2019.