Low back pain from degenerative disc disease (DDD) is one of the most common disorders seen in general and orthopaedic practices. DDD has been attributed to the accumulation of environmental factors, primarily mechanical insults and injuries, imposed on the "normal" aging changes. However, recent studies have shown an association between genetic influences and disc degeneration, with risk of developing DDD quoted to be increased up to six times that of the general population. It is likely that DDD is a complex, multifactorial disease determined by the interplay between gene(s) and the environment. This review focuses on the evidence for genetic disposition, the genes or biological processes that are implicated, and the need to consolidate resources and clarify phenotype definition to take advantage of the new technologies in genetic analysis to enhance our understanding of this condition.