The differential diagnosis of acute inflammatory transverse myelitis (ATM) is broad. Therefore, physicians must be aware of the many potential etiologies for acute myelopathy, and should pursue an ordered, efficient, and cost-effective approach to the diagnosis based on the patient's clinical history, examination, and magnetic resonance imaging (MRI) findings. Clinical, immunological, and radiological findings of non-compressive myelopathies are reviewed, as are how these findings can be used to distinguish between demyelinating, infectious, other inflammatory, vascular, neoplastic, and paraneoplastic etiologies. We also review predictors of further episodes of ATM in patients with demyelinating disorders. We discuss the diagnostic clues and pitfalls of the not uncommon clinical scenario of a presumed "myelopathy with normal MRI." Finally, we suggest an algorithm for the diagnosis and management of acute myelopathies.