Low back pain resulting from intervertebral disk degeneration is a cause of substantial disability and productivity loss. Over the past few years, growing evidence exists which suggests that low-grade bacterial infection, particularly infection with Cutibacterium acnes, may be associated with degenerative disk disease in the lumbar spine. Positive cultures are obtained in approximately 30% of intervertebral disk specimens removed at the time of surgery. In addition, one randomized trial has shown that antibiotic therapy for low back pain in patients with disk degeneration can slow the progression of degeneration and improve pain and disability levels. Although these results are encouraging, the link between infection and disk degeneration remains controversial. Investigators have attempted to address the limitations of clinical research by using translational methods and animal models. These methods have shown that seeding of the disk with bacteria can lead to increased local inflammation and an in vivo phenotype that is similar to human disk degeneration. This review seeks to provide an overview of the clinical, translational, and animal model data linking infection to disk degeneration. We review mechanisms for disk degeneration in the setting of infection and explore areas for future investigation.