The practice of equine neurology has special challenges posed by the size of the animal being examined. Many diagnostic procedures routinely used in small animal practice are unsafe when applied to the equine patient or unavailable to the equine practitioner. Therefore, astute observation is the mainstay of making a neuroanatomic diagnosis, and detailed evidence on the deficits present may be difficult to obtain. Because clinical observation can sometimes be ambiguous and somewhat subjective, it is even more important to approach equine neurology from an evidence-based point of view. Here, such an approach is outlined for the diagnosis of cervical vertebral compressive myelopathy (CVCM), one of the most common noninfectious causes of equine neurologic disease. This article is an attempt to summarize all aspects of making a diagnosis of CVCM on the basis of signalment, clinical examination, ancillary diagnostic tests, and pathologic examination. Each of these considerations has inherent limitations regarding diagnostic accuracy, which are discussed.