Biochemical mechanisms to explain pain generation began relatively recently. Evaluating pain originating from the spine can be challenging because no historical or physical examination findings are sufficiently sensitive or specific for identifying each of the myriad of potential pain generators. These discrete anatomic structures include the nerve root, disc annulus, posterior longitudinal ligament, sacroiliac joint, and facet joint. The diagnostic selective nerve root block is a useful test to determine the etiology of pain when other testing is inconclusive. If a patient with radicular symptoms has non-corroborative visual anatomic and neurophysiologic testing, diagnostic selective nerve root block may elucidate the level of pain generation. Also, in a patient with multiple abnormalities on visual anatomic testing, the lesion of clinical significance can be identified. However, this test may not be necessary in the patient when the specific radiculopathy level diagnosis is apparent; this is the case when a characteristic history and physical examination have a corroborative single-level imaging lesion. Determining which level is generating symptoms has implications for subsequent physical therapy, therapeutic injections, and surgery. This review of selective nerve root blocks describes the relevant anatomy, pathophysiology, rationale, clinical utility, and complications.