The intervertebral disc’s (IVD’s) well-defined microstructural organization and biochemical composition are affected by aging molecular mechanisms and can ultimately lead to a cell-mediated structural failure. The nucleus pulposus changes from gelatinous to a more fibrous structure, cracks and fissures often occur, namely in the annulus fibrosus, and there is a decrease in IVD water content. IVD cells can secrete proinflammatory cytokines to induce and enhance inflammation, and an inflammatory response occurs not only in the IVD but also in the surrounding tissues. The role of microRNAs and their potential as biomarkers for early diagnosis of IVD degeneration has lately drawn great attention. The modulation and balance of anabolic and anticatabolic responses of IVD cells addressing the aberrant cytokine-rich/proinflammatory degenerative IVD environment are the main target of the molecular therapies proposed so far. Growth factors have shown overall to enhance extracellular matrix production and to stimulate IVD cell proliferation.