Low back pain is a leading cause of morbidity in developed societies and is strongly linked to degeneration of the intervertebral disc. The central nucleus pulposus (NP) region is most severely affected during disc degeneration and, consequently, is a focus for novel cell-based regenerative strategies. However, in order to develop such techniques, it is essential to first understand the biology and phenotype of the NP cells intended for repair. Microarray studies have highlighted novel NP markers that will allow a more accurate identification of cells for implantation, and along with other studies, have also revealed the potential importance of a developmental or immature NP cell phenotype in disseminating the optimal cell type for use. Additionally, the degenerative intervertebral disc is a harsh native environment and the effects of this on cells intended for implantation have yet to be fully elucidated; this is crucial for clinical translation of tissue engineered cell-based therapies.