Successful treatment of a patient's spine-related pain depends on accurate targeting of its location and cause. At a basic level, a focused history and physical examination is essential. Understanding of spine anatomy, in particular, spine innervation, is fundamental. Correlation with preprocedure imaging is important to confirm the suspected location(s) of the pain generator and is helpful in planning the approach for image-guided treatment. Understanding the variations in spine anatomy, subtle imaging features, or correlates of root irritation and factors that can affect the patient's presentation at the time of treatment are also critical to accurate targeting and effective treatment. This section reviews the fundamental elements that play a role in accurate diagnosis of the cause of a patient's spine-related pain. Routine application of these basic principles should aid in the approach to the spine-related pain patient and improve both accurate targeting of a patient's pain generator and the outcomes of image-guided treatment.