Discogenic lower back pain (DLBP) is the most common type of chronic lower back pain (LBP), accounting for 39% of cases, compared to 30% of cases due to disc herniation, and even lower prevalence rates for other causes, such as zygapophysial joint pain. Only a small proportion (approximately 20%) of LBP cases can be attributed with reasonable certainty to a pathologic or anatomical entity. Thus, diagnosing the cause of LBP represents the biggest challenge for doctors in this field. In this review, we summarize the process of obtaining a clinical diagnosis of DLBP and discuss the potential for serum-based diagnosis in the near future. The use of serum biomarkers to diagnose DLBP is likely to increase the ease of diagnosis as well as produce more accurate and reproducible results.