Degenerative intervertebral disc disease (IVDD) is one of the main spinal surgery, conditions, which markedly increases the incidence of low back pain and deteriorates the patient’s quality of life, and it imposes significant social and economic burdens. The molecular pathology of IVDD is highly complex and multilateral however still not ompletely understood. New findings indicate that IVDD is closely associated with inflammation, oxidative stress, cell injury and extracellular matrix metabolismdysregulation. Symptomatic management is the main therapeutic approach adopted for IVDD, but it fails to address the basic pathological changes and the causes of the disease. However, research is still focusing on molecular aspects in terms of gene expression, growth factors and cell signaling pathways in an attempt to identify specific molecular targets for IVDD treatment. The paper summarizes the most recent achievements in molecularunderstanding of the pathogenesis of IVDD and gives evidence-based recommendations for clinical practice.