Intervertebral disk degeneration has been considered an irreversible process characterized by a decrease in cell viability, attenuation of proteoglycan and type II collagen synthesis, and dehydration of nucleus pulposus. Stem cell therapy specifically addresses the degenerative process and offers a potentially effective treatment modality. Current preclinical studies show that mesenchymal stem cells have the capacity to repair degenerative disks by differentiation toward chondrocyte-like cells, which produce proteoglycans and type II collagen. There has been evidence that mesenchymal stem cell transplantation into the intervertebral disk increases the intradiskal magnetic resonance imaging T2 signal intensity, increases the disk height, and decreases the degenerative grade in animal models. Appropriate selection of cell carriers/matrix is important because it may prevent cell leakage into the spinal canal and provide an environment that facilitates cell proliferation and differentiation. Although human cell therapy trials for degenerative disk disease are on the horizon, potential issues might arise. The authors hereby review the current state of regenerative cell therapy in degenerative disk disease, with emphasis in cell source, techniques for cellular expansion, induction, transplantation, potential benefit, and risks of the use of this novel medical armamentarium in the treatment of degenerative disk disease.