Low back pain (LBP) is one of the most common disabling symptoms affecting the adult population throughout the industrialized world. The main cause underlying this condition is intervertebral disc degeneration (IDD), which is characterized by progressive decrease of the proteoglycan content within the nucleus pulposus (NP), leading to disc dehydration and loss of its morpho-functional and biomechanical properties. To date, LBP treatment is based upon conservative and invasive procedures which are not capable of restoring the degenerative alterations of the disc, as they only help relieve the symptoms and/or slow down disc degeneration and are, nonetheless, characterized by significant comorbidities, costs and secondary risks. The potential use of different mesenchymal stem/stromal cells (MSCs) for treating IDD has been promisingly tested in vitro and in vivo. The combination of different cell types, preconditioning culture conditions, engineered scaffolds and delivery systems have yielded proof of disc matrix reconstitution, increased cell viability and tissue regeneration in several experimental settings. This article reviews the current literature on stem cell-based therapy for IDD and the outcomes that diverse approaches have achieved.