The use of fluoroscopy, computed tomography, and, most recently, ultrasound in the pain clinic all have advanced rapidly, yet there is scant evidence that this improves the safety or efficacy of pain treatment. In this manuscript, the available evidence about the usefulness of diagnostic imaging and image guidance in planning and delivering pain treatment is critically reviewed. The use of image guidance has become a routine and integral component of pain treatment; however, there is insufficient scientific evidence to judge whether this has improved safety. The logical appeal is overwhelming, to the point that it is now unlikely that scientific comparisons of most techniques with and without radiographic guidance will ever be conducted. This analysis can serve to guide future investigators who set out to understand how to apply new imaging techniques, and in the process, how to rigorously evaluate their usefulness.