Given the genetic and proteomic advances of the past decade, understanding of the molecular etiopathogenesis of several complex diseases is increasing. Intervertebral disc disease (IVDD) is no different from other complex diseases where both environmental and genetic constituents are considered causes. This concept has challenged the traditional view that age, occupation, smoking, obesity, and primarily wear and tear are the only sources of disc degeneration.We conducted a systematic Medline review of the most current articles related to gene involvement in the development of IVDD in humans.Candidate gene linkage and association studies involving the functional components of the intervertebral disc, including collagen I, collagen IX, collagen XI, aggrecan, extracellular matrix-degrading enzymes, inflammatory cytokines (IL-1, IL-6, and TNFα), Fas/FasL and vitamin D receptors, have had promising results.This review emphasizes the latest advances in gene association with specific degenerated disc phenotypes, single nucleotide polymorphisms, disease heredity, and gene-environmental interactions in relation to IVDD to help improve future studies related to the genetic mechanisms underlying IVDD.