Background and Aims Dysfunction of physiological regulation systems may underlie the disrupted emotional and self-regulatory processes among people with substance use disorder (SUD). This paper reviews evidence as to whether or not respiratory sinus arrhythmia (RSA), as a psychophysiological index of emotional regulation, could provide useful information in treatment-outcome research to provide insights into recovery processes. Methods We reviewed the use of RSA in clinical research and studies on SUD treatment. Search terms for the review of RSA in clinical research included respiratory sinus arrhythmia, heart rate variability, vagal, cardiac vagal control, psychophysiology, intervention, treatment, mindfulness, mind-body, mental health, substance use, chemical dependence, regulation and emotion regulation. For the review of RSA in intervention studies, we included only those that provided adequate description of psychophysiological methods, and examined RSA in the context of an intervention study. Results RSA appears to be able to provide an index of self-regulatory capacity; however, it has been little used in either intervention or treatment research. Of the four intervention studies included in this review, all were mindfulness-based interventions. Two studies were with substance using samples, and both showed pre-post increases in RSA and related improved substance use outcomes. Two of the three studies were randomized controlled trials (RCTs), and both showed significant increases in RSA in the experimental compared to comparison condition. Conclusion Respiratory sinus arrhythmiamay be a useful index of emotional regulation in people with substance use disorder, and a potential measure of underlying mechanisms for SUD treatment studies, particularly mindfulness-based interventions. [ABSTRACT FROM AUTHOR]