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Microvascular ischemia is a frequent cause of acute isolated cranial nerve six (CN VI) palsy. Alternative etiologies of CN VI palsy with grave neurological implications often cannot be excluded without neuroimaging. However, the practice of obtaining neuro-imaging for every patient presenting with an acute, isolated CN VI palsy is a costly diagnostic paradigm. Recent studies have sought to delineate the risk factors for microvascular ischemic ocular motor cranial neuropathies and to investigate the utility of neuroimaging in the initial evaluation of such cases. The aim of this review is to provide an update on the issues and controversies of neuroimaging in the initial evaluation of an acute isolated CN VI palsy.Diabetes mellitus, but not hypertension alone, is a risk factor for microvascular ischemic ocular motor cranial neuropathies. Small-scale prospective studies have suggested that immediate neuroimaging should be considered in the initial evaluation of all patients with CN VI palsy, regardless of the presence of microvascular ischemic risk factors.There remains a lack of large-scale, prospective, age-specific studies to indicate the diagnostic yield of immediate neuroimaging in the setting of acute isolated CN VI palsy. An algorithm is offered for the evaluation of acute isolated CN VI palsy, which allows for initial expectant observation and re-consideration of obtaining neuroimaging upon follow-up if the ophthalmoplegia does not improve, progresses, or becomes nonisolated.