© 2016 Elsevier Ltd Back pain is the most common cause of pain and disability worldwide. While its etiology remains unknown, it is typically associated with intervertebral disc (IVD) degeneration. Despite the prevalence of back pain, relatively little is known about the specific cellular pathways and mechanisms that contribute to the development, function and degeneration of the IVD. Consequently, current treatments for back pain are largely limited to symptomatic interventions. However, major progress is being made in multiple research directions to unravel the biology and pathology of the IVD, raising hope that effective disease-modifying interventions will soon be developed. In this review, we will discuss our current knowledge and gaps in knowledge on the developmental origin of the IVD, the phenotype of the distinct cell types found within the IVD tissues, molecular targets in IVD degeneration identified using bioinformatics strategies, and mechanotransduction pathways that influence IVD cell fate and function.