Modic changes, particularly type 1, represent a significant clinical and radiologic challenge in chronic low back pain. This review evaluates the infectious hypothesis, suggesting that the colonization of the intervertebral disk by low-virulence pathogens (primarily Cutibacterium acnes) may contribute to the pathogenesis of these lesions. The evolution of this concept is analyzed through the results of pivotal clinical trials, highlighting the landmark perspectives provided by the Modic Antibiotic Spine Therapy study while considering the methodological nuances and divergent findings introduced by the Antibiotics in Modic Changes study. The article also examines the evidence from disk biopsy studies, addressing the technical difficulties in distinguishing true microbial colonization from potential sample contamination. Finally, we propose an integrative model where mechanical and infectious factors interact, suggesting that bone marrow inflammation may reflect a localized immune response to intradiskal bacterial presence. This balanced approach calls for the standardization of future research protocols to clarify the role of targeted therapeutic interventions.