Magnetic resonance (MR) imaging in patients with persistent low back pain and sciatica effectively demonstrates spine anatomy and the relationship of nerve roots and intervertebral disks. Except in cases with nerve root compression, disk extrusion, or central stenosis, conventional anatomic MR images do not help distinguish effectively between painful and nonpainful degenerating disks. Hypoxia, inflammation, innervation, accelerated catabolism, and reduced water and glycosaminoglycan content characterize degenerated disks, the extent of which may distinguish nonpainful from painful ones. Applied to the spine, "functional" imaging techniques such as MR spectroscopy, T1ρ calculation, T2 relaxation time measurement, diffusion quantitative imaging, and radio nucleotide imaging provide measurements of some of these degenerative features. Novel minimally invasive therapies, with injected growth factors or genetic materials, target these processes in the disk and effectively reverse degeneration in controlled laboratory conditions. Functional imaging has applications in clinical trials to evaluate the efficacy of these therapies and eventually to select patients for treatment. This report summarizes the biochemical processes in disk degeneration, the application of advanced disk imaging techniques, and the novel biologic therapies that presently have the most clinical promise.