Patients with lateral medullary syndrome classically present with crossed hemisensory disturbance, ipsilateral Horner syndrome, and cerebellar signs, all of which are attributable to infarction of the lateral medulla. However, variability in the presentation of this syndrome is the rule, as illustrated in this case presentation and literature review. We propose an approach to diagnosis and management of the lateral medullary syndrome and illustrate the need to integrate clinical information with an understanding of brainstem anatomy with the goal of determining which patients require urgent neuroimaging and acute stroke therapies. The importance of recognition of this condition in the emergency department is underscored by the association between lateral medullary infarction and vertebral artery dissection. With optimal therapy, the prognosis for recovery from lateral medullary syndrome is good.