Chronic pain is a widespread health condition affecting millions of individuals worldwide. Despite its high prevalence, the underlying neural mechanisms and pathophysiology of chronic pain are still not well understood. Introduced about 35 years ago, brain diffusion MRI has emerged as a powerful tool to investigate white matter microstructure and connectivity changes in chronic pain conditions. In this review, we provide an overview of the current state of research on brain diffusion MRI in chronic pain, including the methods used to acquire and analyze diffusion MRI data, as well as the major findings in the field. We discuss the evidence supporting the role of altered white matter microstructure and connectivity in chronic pain conditions, highlighting the importance of studying multiple chronic pain syndromes to identify common neurobiological pathways. We also explore the potential clinical applications of diffusion MRI in chronic pain research, such as identifying biomarkers for diagnosis and treatment response. In addition, we explore the shortcomings and difficulties associated with brain diffusion MRI in chronic pain studies, such as the necessity for uniformity in data acquisition and analysis methods. Finally, we discuss emerging techniques and future directions in brain diffusion MRI research that may provide new insights into the pathophysiology of chronic pain and potential new therapeutic targets. In summary, we are optimistic that brain diffusion MRI has significant potential in furthering our knowledge of chronic pain and enhancing clinical outcomes, although further research is required due to the limited body of literature currently available, and that targeted therapeutic strategies are yet to be identified.