Myelitis is a rare neurological disorder of the spinal cord that is caused by inflammation and can have devastating neurologic effects with up to two-thirds of patients having a moderate to severe degree of residual disability. Symptoms typically develop over hours or days and then worsen over a matter of days to weeks. Patients can present with sensory alteration, weakness, and autonomic dysfunction including bowel and bladder problems, temperature dysregulation, or even bouts of hypertension. Evaluation for compressive etiologies must be a priority as compressive myelopathy and transverse myelitis are often clinically indistinguishable and emergent surgical intervention is indicated in such cases. However, if neuroimaging and CSF studies indicate inflammation within the central nervous system, then a work-up for myelitis must include autoimmune, inflammatory, and infectious etiologies. Acute management of these patients is dictated by which etiology is suspected and rapid initiation of that treatment portends a more favorable patient outcome. This review will discuss a practical clinical approach to the diagnosis and acute management of patients with myelitis including clinical symptoms, the role of neuroimaging, and the utility of both CSF and serological studies in the management of these patients.